Modulation of Lymphocyte Potassium Channel KV1.3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.
Identifieur interne : 000108 ( Main/Exploration ); précédent : 000107; suivant : 000109Modulation of Lymphocyte Potassium Channel KV1.3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.
Auteurs : Seow Theng Ong ; Saumya Bajaj ; Mark R. Tanner [États-Unis] ; Shih Chieh Chang ; Bankala Krishnarjuna [Australie] ; Xuan Rui Ng ; Rodrigo A V. Morales [Australie] ; Ming Wei Chen ; Dahai Luo ; Dharmeshkumar Patel [Australie] ; Sabina Yasmin [Australie] ; Jeremy Jun Heng Ng ; Zhong Zhuang ; Hai M. Nguyen [États-Unis] ; Abbas El Sahili ; Julien Lescar ; Rahul Patil [Australie] ; Susan A. Charman [Australie] ; Edward G. Robins ; Julian L. Goggi ; Peng Wen Tan ; Pragalath Sadasivam ; Boominathan Ramasamy ; Siddana V. Hartimath ; Vikas Dhawan [États-Unis] ; Janna Bednenko [États-Unis] ; Paul Colussi [États-Unis] ; Heike Wulff [États-Unis] ; Michael W. Pennington [États-Unis] ; Serdar Kuyucak [Australie] ; Raymond S. Norton [Australie] ; Christine Beeton [États-Unis] ; K George ChandySource :
- ACS pharmacology & translational science [ 2575-9108 ] ; 2020.
Abstract
We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated KV1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to KV1.3, causing current run-down by a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. EgK5 exhibits selectivity for KV1.3 over other channels, receptors, transporters, and enzymes. EgK5 suppresses antigen-triggered proliferation of effector memory T cells, a subset enriched among pathogenic autoreactive T cells in autoimmune disease. PET-CT imaging with 18F-labeled EgK5 shows accumulation of the peptide in large and small joints of rodents. In keeping with its arthrotropism, EgK5 treats disease in a rat model of rheumatoid arthritis. It was also effective in treating disease in a rat model of atopic dermatitis. No signs of toxicity are observed at 10-100 times the in vivo dose. EgK5 shows promise for clinical development as a therapeutic for autoimmune diseases.
DOI: 10.1021/acsptsci.0c00035
PubMed: 32832873
PubMed Central: PMC7432667
Affiliations:
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Tanner</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030</wicri:regionArea><wicri:noRegion>Texas 77030</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Shih Chieh" sort="Chang, Shih Chieh" uniqKey="Chang S" first="Shih Chieh" last="Chang">Shih Chieh Chang</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Krishnarjuna, Bankala" sort="Krishnarjuna, Bankala" uniqKey="Krishnarjuna B" first="Bankala" last="Krishnarjuna">Bankala Krishnarjuna</name><affiliation wicri:level="1"><nlm:affiliation>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Ng, Xuan Rui" sort="Ng, Xuan Rui" uniqKey="Ng X" first="Xuan Rui" last="Ng">Xuan Rui Ng</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Morales, Rodrigo A V" sort="Morales, Rodrigo A V" uniqKey="Morales R" first="Rodrigo A V" last="Morales">Rodrigo A V. Morales</name><affiliation wicri:level="1"><nlm:affiliation>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Ming Wei" sort="Chen, Ming Wei" uniqKey="Chen M" first="Ming Wei" last="Chen">Ming Wei Chen</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Luo, Dahai" sort="Luo, Dahai" uniqKey="Luo D" first="Dahai" last="Luo">Dahai Luo</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Patel, Dharmeshkumar" sort="Patel, Dharmeshkumar" uniqKey="Patel D" first="Dharmeshkumar" last="Patel">Dharmeshkumar Patel</name><affiliation wicri:level="4"><nlm:affiliation>School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Physics, University of Sydney, Sydney, New South Wales 2006</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Yasmin, Sabina" sort="Yasmin, Sabina" uniqKey="Yasmin S" first="Sabina" last="Yasmin">Sabina Yasmin</name><affiliation wicri:level="4"><nlm:affiliation>School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Physics, University of Sydney, Sydney, New South Wales 2006</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Ng, Jeremy Jun Heng" sort="Ng, Jeremy Jun Heng" uniqKey="Ng J" first="Jeremy Jun Heng" last="Ng">Jeremy Jun Heng Ng</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Zhuang, Zhong" sort="Zhuang, Zhong" uniqKey="Zhuang Z" first="Zhong" last="Zhuang">Zhong Zhuang</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Nguyen, Hai M" sort="Nguyen, Hai M" uniqKey="Nguyen H" first="Hai M" last="Nguyen">Hai M. Nguyen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology, University of California, Davis, California 95616, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology, University of California, Davis, California 95616</wicri:regionArea><wicri:noRegion>California 95616</wicri:noRegion></affiliation></author><author><name sortKey="El Sahili, Abbas" sort="El Sahili, Abbas" uniqKey="El Sahili A" first="Abbas" last="El Sahili">Abbas El Sahili</name><affiliation><nlm:affiliation>School of Biological Sciences, Nanyang Institute of Structural Biology, Experimental Medicine building, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Lescar, Julien" sort="Lescar, Julien" uniqKey="Lescar J" first="Julien" last="Lescar">Julien Lescar</name><affiliation><nlm:affiliation>School of Biological Sciences, Nanyang Institute of Structural Biology, Experimental Medicine building, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Patil, Rahul" sort="Patil, Rahul" uniqKey="Patil R" first="Rahul" last="Patil">Rahul Patil</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Charman, Susan A" sort="Charman, Susan A" uniqKey="Charman S" first="Susan A" last="Charman">Susan A. Charman</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Robins, Edward G" sort="Robins, Edward G" uniqKey="Robins E" first="Edward G" last="Robins">Edward G. Robins</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, NUS Clinical Imaging Research Centre (CIRC), Centre for Life Sciences, Singapore 117599.</nlm:affiliation><wicri:noCountry code="subField">Singapore 117599</wicri:noCountry></affiliation></author><author><name sortKey="Goggi, Julian L" sort="Goggi, Julian L" uniqKey="Goggi J" first="Julian L" last="Goggi">Julian L. Goggi</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Tan, Peng Wen" sort="Tan, Peng Wen" uniqKey="Tan P" first="Peng Wen" last="Tan">Peng Wen Tan</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Sadasivam, Pragalath" sort="Sadasivam, Pragalath" uniqKey="Sadasivam P" first="Pragalath" last="Sadasivam">Pragalath Sadasivam</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Ramasamy, Boominathan" sort="Ramasamy, Boominathan" uniqKey="Ramasamy B" first="Boominathan" last="Ramasamy">Boominathan Ramasamy</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Hartimath, Siddana V" sort="Hartimath, Siddana V" uniqKey="Hartimath S" first="Siddana V" last="Hartimath">Siddana V. Hartimath</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Dhawan, Vikas" sort="Dhawan, Vikas" uniqKey="Dhawan V" first="Vikas" last="Dhawan">Vikas Dhawan</name><affiliation wicri:level="1"><nlm:affiliation>Peptides International, Inc., Louisville, Kentucky 40269, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Peptides International, Inc., Louisville, Kentucky 40269</wicri:regionArea><wicri:noRegion>Kentucky 40269</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>AmbioPharm Inc., North Augusta, South Carolina 29842, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>AmbioPharm Inc., North Augusta, South Carolina 29842</wicri:regionArea><wicri:noRegion>South Carolina 29842</wicri:noRegion></affiliation></author><author><name sortKey="Bednenko, Janna" sort="Bednenko, Janna" uniqKey="Bednenko J" first="Janna" last="Bednenko">Janna Bednenko</name><affiliation wicri:level="1"><nlm:affiliation>TetraGenetics Inc, Arlington, Massachusetts 02474, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>TetraGenetics Inc, Arlington, Massachusetts 02474</wicri:regionArea><wicri:noRegion>Massachusetts 02474</wicri:noRegion></affiliation></author><author><name sortKey="Colussi, Paul" sort="Colussi, Paul" uniqKey="Colussi P" first="Paul" last="Colussi">Paul Colussi</name><affiliation wicri:level="1"><nlm:affiliation>TetraGenetics Inc, Arlington, Massachusetts 02474, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>TetraGenetics Inc, Arlington, Massachusetts 02474</wicri:regionArea><wicri:noRegion>Massachusetts 02474</wicri:noRegion></affiliation></author><author><name sortKey="Wulff, Heike" sort="Wulff, Heike" uniqKey="Wulff H" first="Heike" last="Wulff">Heike Wulff</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology, University of California, Davis, California 95616, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology, University of California, Davis, California 95616</wicri:regionArea><wicri:noRegion>California 95616</wicri:noRegion></affiliation></author><author><name sortKey="Pennington, Michael W" sort="Pennington, Michael W" uniqKey="Pennington M" first="Michael W" last="Pennington">Michael W. Pennington</name><affiliation wicri:level="1"><nlm:affiliation>Peptides International, Inc., Louisville, Kentucky 40269, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Peptides International, Inc., Louisville, Kentucky 40269</wicri:regionArea><wicri:noRegion>Kentucky 40269</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>AmbioPharm Inc., North Augusta, South Carolina 29842, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>AmbioPharm Inc., North Augusta, South Carolina 29842</wicri:regionArea><wicri:noRegion>South Carolina 29842</wicri:noRegion></affiliation></author><author><name sortKey="Kuyucak, Serdar" sort="Kuyucak, Serdar" uniqKey="Kuyucak S" first="Serdar" last="Kuyucak">Serdar Kuyucak</name><affiliation wicri:level="4"><nlm:affiliation>School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Physics, University of Sydney, Sydney, New South Wales 2006</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Norton, Raymond S" sort="Norton, Raymond S" uniqKey="Norton R" first="Raymond S" last="Norton">Raymond S. Norton</name><affiliation wicri:level="1"><nlm:affiliation>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>ARC Centre for Fragment-Based Design, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ARC Centre for Fragment-Based Design, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Beeton, Christine" sort="Beeton, Christine" uniqKey="Beeton C" first="Christine" last="Beeton">Christine Beeton</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030</wicri:regionArea><wicri:noRegion>Texas 77030</wicri:noRegion></affiliation></author><author><name sortKey="Chandy, K George" sort="Chandy, K George" uniqKey="Chandy K" first="K George" last="Chandy">K George Chandy</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32832873</idno><idno type="pmid">32832873</idno><idno type="doi">10.1021/acsptsci.0c00035</idno><idno type="pmc">PMC7432667</idno><idno type="wicri:Area/Main/Corpus">000136</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000136</idno><idno type="wicri:Area/Main/Curation">000136</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000136</idno><idno type="wicri:Area/Main/Exploration">000136</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Modulation of Lymphocyte Potassium Channel K<sub>V</sub>1.3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.</title><author><name sortKey="Ong, Seow Theng" sort="Ong, Seow Theng" uniqKey="Ong S" first="Seow Theng" last="Ong">Seow Theng Ong</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Bajaj, Saumya" sort="Bajaj, Saumya" uniqKey="Bajaj S" first="Saumya" last="Bajaj">Saumya Bajaj</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Tanner, Mark R" sort="Tanner, Mark R" uniqKey="Tanner M" first="Mark R" last="Tanner">Mark R. Tanner</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030</wicri:regionArea><wicri:noRegion>Texas 77030</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Shih Chieh" sort="Chang, Shih Chieh" uniqKey="Chang S" first="Shih Chieh" last="Chang">Shih Chieh Chang</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Krishnarjuna, Bankala" sort="Krishnarjuna, Bankala" uniqKey="Krishnarjuna B" first="Bankala" last="Krishnarjuna">Bankala Krishnarjuna</name><affiliation wicri:level="1"><nlm:affiliation>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Ng, Xuan Rui" sort="Ng, Xuan Rui" uniqKey="Ng X" first="Xuan Rui" last="Ng">Xuan Rui Ng</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Morales, Rodrigo A V" sort="Morales, Rodrigo A V" uniqKey="Morales R" first="Rodrigo A V" last="Morales">Rodrigo A V. Morales</name><affiliation wicri:level="1"><nlm:affiliation>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Ming Wei" sort="Chen, Ming Wei" uniqKey="Chen M" first="Ming Wei" last="Chen">Ming Wei Chen</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Luo, Dahai" sort="Luo, Dahai" uniqKey="Luo D" first="Dahai" last="Luo">Dahai Luo</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Patel, Dharmeshkumar" sort="Patel, Dharmeshkumar" uniqKey="Patel D" first="Dharmeshkumar" last="Patel">Dharmeshkumar Patel</name><affiliation wicri:level="4"><nlm:affiliation>School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Physics, University of Sydney, Sydney, New South Wales 2006</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Yasmin, Sabina" sort="Yasmin, Sabina" uniqKey="Yasmin S" first="Sabina" last="Yasmin">Sabina Yasmin</name><affiliation wicri:level="4"><nlm:affiliation>School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Physics, University of Sydney, Sydney, New South Wales 2006</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Ng, Jeremy Jun Heng" sort="Ng, Jeremy Jun Heng" uniqKey="Ng J" first="Jeremy Jun Heng" last="Ng">Jeremy Jun Heng Ng</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Zhuang, Zhong" sort="Zhuang, Zhong" uniqKey="Zhuang Z" first="Zhong" last="Zhuang">Zhong Zhuang</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Nguyen, Hai M" sort="Nguyen, Hai M" uniqKey="Nguyen H" first="Hai M" last="Nguyen">Hai M. Nguyen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology, University of California, Davis, California 95616, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology, University of California, Davis, California 95616</wicri:regionArea><wicri:noRegion>California 95616</wicri:noRegion></affiliation></author><author><name sortKey="El Sahili, Abbas" sort="El Sahili, Abbas" uniqKey="El Sahili A" first="Abbas" last="El Sahili">Abbas El Sahili</name><affiliation><nlm:affiliation>School of Biological Sciences, Nanyang Institute of Structural Biology, Experimental Medicine building, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Lescar, Julien" sort="Lescar, Julien" uniqKey="Lescar J" first="Julien" last="Lescar">Julien Lescar</name><affiliation><nlm:affiliation>School of Biological Sciences, Nanyang Institute of Structural Biology, Experimental Medicine building, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author><author><name sortKey="Patil, Rahul" sort="Patil, Rahul" uniqKey="Patil R" first="Rahul" last="Patil">Rahul Patil</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Charman, Susan A" sort="Charman, Susan A" uniqKey="Charman S" first="Susan A" last="Charman">Susan A. Charman</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Robins, Edward G" sort="Robins, Edward G" uniqKey="Robins E" first="Edward G" last="Robins">Edward G. Robins</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, NUS Clinical Imaging Research Centre (CIRC), Centre for Life Sciences, Singapore 117599.</nlm:affiliation><wicri:noCountry code="subField">Singapore 117599</wicri:noCountry></affiliation></author><author><name sortKey="Goggi, Julian L" sort="Goggi, Julian L" uniqKey="Goggi J" first="Julian L" last="Goggi">Julian L. Goggi</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Tan, Peng Wen" sort="Tan, Peng Wen" uniqKey="Tan P" first="Peng Wen" last="Tan">Peng Wen Tan</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Sadasivam, Pragalath" sort="Sadasivam, Pragalath" uniqKey="Sadasivam P" first="Pragalath" last="Sadasivam">Pragalath Sadasivam</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Ramasamy, Boominathan" sort="Ramasamy, Boominathan" uniqKey="Ramasamy B" first="Boominathan" last="Ramasamy">Boominathan Ramasamy</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Hartimath, Siddana V" sort="Hartimath, Siddana V" uniqKey="Hartimath S" first="Siddana V" last="Hartimath">Siddana V. Hartimath</name><affiliation><nlm:affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138667</wicri:noCountry></affiliation></author><author><name sortKey="Dhawan, Vikas" sort="Dhawan, Vikas" uniqKey="Dhawan V" first="Vikas" last="Dhawan">Vikas Dhawan</name><affiliation wicri:level="1"><nlm:affiliation>Peptides International, Inc., Louisville, Kentucky 40269, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Peptides International, Inc., Louisville, Kentucky 40269</wicri:regionArea><wicri:noRegion>Kentucky 40269</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>AmbioPharm Inc., North Augusta, South Carolina 29842, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>AmbioPharm Inc., North Augusta, South Carolina 29842</wicri:regionArea><wicri:noRegion>South Carolina 29842</wicri:noRegion></affiliation></author><author><name sortKey="Bednenko, Janna" sort="Bednenko, Janna" uniqKey="Bednenko J" first="Janna" last="Bednenko">Janna Bednenko</name><affiliation wicri:level="1"><nlm:affiliation>TetraGenetics Inc, Arlington, Massachusetts 02474, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>TetraGenetics Inc, Arlington, Massachusetts 02474</wicri:regionArea><wicri:noRegion>Massachusetts 02474</wicri:noRegion></affiliation></author><author><name sortKey="Colussi, Paul" sort="Colussi, Paul" uniqKey="Colussi P" first="Paul" last="Colussi">Paul Colussi</name><affiliation wicri:level="1"><nlm:affiliation>TetraGenetics Inc, Arlington, Massachusetts 02474, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>TetraGenetics Inc, Arlington, Massachusetts 02474</wicri:regionArea><wicri:noRegion>Massachusetts 02474</wicri:noRegion></affiliation></author><author><name sortKey="Wulff, Heike" sort="Wulff, Heike" uniqKey="Wulff H" first="Heike" last="Wulff">Heike Wulff</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacology, University of California, Davis, California 95616, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology, University of California, Davis, California 95616</wicri:regionArea><wicri:noRegion>California 95616</wicri:noRegion></affiliation></author><author><name sortKey="Pennington, Michael W" sort="Pennington, Michael W" uniqKey="Pennington M" first="Michael W" last="Pennington">Michael W. Pennington</name><affiliation wicri:level="1"><nlm:affiliation>Peptides International, Inc., Louisville, Kentucky 40269, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Peptides International, Inc., Louisville, Kentucky 40269</wicri:regionArea><wicri:noRegion>Kentucky 40269</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>AmbioPharm Inc., North Augusta, South Carolina 29842, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>AmbioPharm Inc., North Augusta, South Carolina 29842</wicri:regionArea><wicri:noRegion>South Carolina 29842</wicri:noRegion></affiliation></author><author><name sortKey="Kuyucak, Serdar" sort="Kuyucak, Serdar" uniqKey="Kuyucak S" first="Serdar" last="Kuyucak">Serdar Kuyucak</name><affiliation wicri:level="4"><nlm:affiliation>School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Physics, University of Sydney, Sydney, New South Wales 2006</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Norton, Raymond S" sort="Norton, Raymond S" uniqKey="Norton R" first="Raymond S" last="Norton">Raymond S. Norton</name><affiliation wicri:level="1"><nlm:affiliation>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>ARC Centre for Fragment-Based Design, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>ARC Centre for Fragment-Based Design, Monash University, Parkville, Victoria 3052</wicri:regionArea><wicri:noRegion>Victoria 3052</wicri:noRegion></affiliation></author><author><name sortKey="Beeton, Christine" sort="Beeton, Christine" uniqKey="Beeton C" first="Christine" last="Beeton">Christine Beeton</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030</wicri:regionArea><wicri:noRegion>Texas 77030</wicri:noRegion></affiliation></author><author><name sortKey="Chandy, K George" sort="Chandy, K George" uniqKey="Chandy K" first="K George" last="Chandy">K George Chandy</name><affiliation><nlm:affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</nlm:affiliation><wicri:noCountry code="subField">Singapore 636921</wicri:noCountry></affiliation></author></analytic><series><title level="j">ACS pharmacology & translational science</title><idno type="eISSN">2575-9108</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated K<sub>V</sub>1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to K<sub>V</sub>1.3, causing current run-down by a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. EgK5 exhibits selectivity for K<sub>V</sub>1.3 over other channels, receptors, transporters, and enzymes. EgK5 suppresses antigen-triggered proliferation of effector memory T cells, a subset enriched among pathogenic autoreactive T cells in autoimmune disease. PET-CT imaging with <sup>18</sup>F-labeled EgK5 shows accumulation of the peptide in large and small joints of rodents. In keeping with its arthrotropism, EgK5 treats disease in a rat model of rheumatoid arthritis. It was also effective in treating disease in a rat model of atopic dermatitis. No signs of toxicity are observed at 10-100 times the <i>in vivo</i> dose. EgK5 shows promise for clinical development as a therapeutic for autoimmune diseases.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32832873</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>28</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">2575-9108</ISSN><JournalIssue CitedMedium="Internet"><Volume>3</Volume><Issue>4</Issue><PubDate><Year>2020</Year><Month>Aug</Month><Day>14</Day></PubDate></JournalIssue><Title>ACS pharmacology & translational science</Title><ISOAbbreviation>ACS Pharmacol Transl Sci</ISOAbbreviation></Journal><ArticleTitle>Modulation of Lymphocyte Potassium Channel K<sub>V</sub>1.3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.</ArticleTitle><Pagination><MedlinePgn>720-736</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/acsptsci.0c00035</ELocationID><Abstract><AbstractText>We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated K<sub>V</sub>1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to K<sub>V</sub>1.3, causing current run-down by a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. EgK5 exhibits selectivity for K<sub>V</sub>1.3 over other channels, receptors, transporters, and enzymes. EgK5 suppresses antigen-triggered proliferation of effector memory T cells, a subset enriched among pathogenic autoreactive T cells in autoimmune disease. PET-CT imaging with <sup>18</sup>F-labeled EgK5 shows accumulation of the peptide in large and small joints of rodents. In keeping with its arthrotropism, EgK5 treats disease in a rat model of rheumatoid arthritis. It was also effective in treating disease in a rat model of atopic dermatitis. No signs of toxicity are observed at 10-100 times the <i>in vivo</i> dose. EgK5 shows promise for clinical development as a therapeutic for autoimmune diseases.</AbstractText><CopyrightInformation>Copyright © 2020 American Chemical Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ong</LastName><ForeName>Seow Theng</ForeName><Initials>ST</Initials><AffiliationInfo><Affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bajaj</LastName><ForeName>Saumya</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tanner</LastName><ForeName>Mark R</ForeName><Initials>MR</Initials><AffiliationInfo><Affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Shih Chieh</ForeName><Initials>SC</Initials><AffiliationInfo><Affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Krishnarjuna</LastName><ForeName>Bankala</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ng</LastName><ForeName>Xuan Rui</ForeName><Initials>XR</Initials><AffiliationInfo><Affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morales</LastName><ForeName>Rodrigo A V</ForeName><Initials>RAV</Initials><AffiliationInfo><Affiliation>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Ming Wei</ForeName><Initials>MW</Initials><AffiliationInfo><Affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>Dahai</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Patel</LastName><ForeName>Dharmeshkumar</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yasmin</LastName><ForeName>Sabina</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ng</LastName><ForeName>Jeremy Jun Heng</ForeName><Initials>JJH</Initials><AffiliationInfo><Affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhuang</LastName><ForeName>Zhong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Experimental Medicine Building, 59 Nanyang Drive, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nguyen</LastName><ForeName>Hai M</ForeName><Initials>HM</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, University of California, Davis, California 95616, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El Sahili</LastName><ForeName>Abbas</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>School of Biological Sciences, Nanyang Institute of Structural Biology, Experimental Medicine building, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lescar</LastName><ForeName>Julien</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>School of Biological Sciences, Nanyang Institute of Structural Biology, Experimental Medicine building, Singapore 636921.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Patil</LastName><ForeName>Rahul</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Charman</LastName><ForeName>Susan A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Centre for Drug Candidate Optimisation, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Robins</LastName><ForeName>Edward G</ForeName><Initials>EG</Initials><AffiliationInfo><Affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Singapore Bioimaging Consortium, NUS Clinical Imaging Research Centre (CIRC), Centre for Life Sciences, Singapore 117599.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goggi</LastName><ForeName>Julian L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Peng Wen</ForeName><Initials>PW</Initials><AffiliationInfo><Affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sadasivam</LastName><ForeName>Pragalath</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ramasamy</LastName><ForeName>Boominathan</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hartimath</LastName><ForeName>Siddana V</ForeName><Initials>SV</Initials><AffiliationInfo><Affiliation>Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A Star), Singapore 138667.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dhawan</LastName><ForeName>Vikas</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Peptides International, Inc., Louisville, Kentucky 40269, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>AmbioPharm Inc., North Augusta, South Carolina 29842, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bednenko</LastName><ForeName>Janna</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>TetraGenetics Inc, Arlington, Massachusetts 02474, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Colussi</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>TetraGenetics Inc, Arlington, Massachusetts 02474, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wulff</LastName><ForeName>Heike</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Pharmacology, University of California, Davis, California 95616, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pennington</LastName><ForeName>Michael W</ForeName><Initials>MW</Initials><AffiliationInfo><Affiliation>Peptides International, Inc., Louisville, Kentucky 40269, United States.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>AmbioPharm Inc., North Augusta, South Carolina 29842, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kuyucak</LastName><ForeName>Serdar</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Norton</LastName><ForeName>Raymond S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ARC Centre for Fragment-Based Design, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beeton</LastName><ForeName>Christine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One 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