Inhibition of Viral Adhesion and Infection by Sialic-Acid-Conjugated Dendritic Polymers
Identifieur interne : 000794 ( Istex/Checkpoint ); précédent : 000793; suivant : 000795Inhibition of Viral Adhesion and Infection by Sialic-Acid-Conjugated Dendritic Polymers
Auteurs : Jon D. Reuter [États-Unis] ; Andrzej Myc [États-Unis] ; Michael M. Hayes [États-Unis] ; Zhonghong Gan [États-Unis] ; Rene Roy [États-Unis] ; Dujie Qin [États-Unis] ; Rui Yin [États-Unis] ; Lars T. Piehler [États-Unis] ; Roseita Esfand [États-Unis] ; Donald A. Tomalia [États-Unis] ; James R. Baker [États-Unis]Source :
- Bioconjugate Chemistry [ 1043-1802 ] ; 1999.
Abstract
Multiple sialic acid (SA) residues conjugated to a linear polyacrylamide backbone are more effective than monomeric SA at inhibiting influenza-induced agglutination of red blood cells. However, “polymeric inhibitors” based on polyacrylamide backbones are cytotoxic. Dendritic polymers offer a nontoxic alternative to polyacrylamide and may provide a variety of potential synthetic inhibitors of influenza virus adhesion due to the wide range of available polymer structures. We evaluated several dendritic polymeric inhibitors, including spheroidal, linear, linear-dendron copolymers, comb-branched, and dendrigraft polymers, for the ability to inhibit virus hemagglutination (HA) and to block infection of mammalian cells in vitro. Four viruses were tested: influenza A H2N2 (selectively propagated two ways), X-31 influenza A H3N2, and sendai. The most potent of the linear and spheroidal inhibitors were 32−256-fold more effective than monomeric SA at inhibiting HA by the H2N2 influenza virus. Linear-dendron copolymers were 1025−8200-fold more effective against H2N2 influenza, X-31 influenza, and sendai viruses. The most effective were the comb-branched and dendrigraft inhibitors, which showed up to 50000-fold increased activity against these viruses. We were able to demonstrate significant (p < 0.001) dose-dependent reduction of influenza infection in mammalian cells by polymeric inhibitors, the first such demonstration for multivalent SA inhibitors. Effective dendrimer polymers were not cytotoxic to mammalian cells at therapeutic levels. Of additional interest, variation in the inhibitory effect was observed with different viruses, suggesting possible differences due to specific growth conditions of virus. SA-conjugated dendritic polymers may provide a new therapeutic modality for viruses that employ SA as their target receptor.
Url:
DOI: 10.1021/bc980099n
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
ISTEX:5B1815B5585E4AAEDFF2060DF62E768E50583B6FLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Inhibition of Viral Adhesion and Infection by Sialic-Acid-Conjugated Dendritic Polymers</title><author><name sortKey="Reuter, Jon D" sort="Reuter, Jon D" uniqKey="Reuter J" first="Jon D." last="Reuter">Jon D. Reuter</name></author><author><name sortKey="Myc, Andrzej" sort="Myc, Andrzej" uniqKey="Myc A" first="Andrzej" last="Myc">Andrzej Myc</name></author><author><name sortKey="Hayes, Michael M" sort="Hayes, Michael M" uniqKey="Hayes M" first="Michael M." last="Hayes">Michael M. Hayes</name></author><author><name sortKey="Gan, Zhonghong" sort="Gan, Zhonghong" uniqKey="Gan Z" first="Zhonghong" last="Gan">Zhonghong Gan</name></author><author><name sortKey="Roy, Rene" sort="Roy, Rene" uniqKey="Roy R" first="Rene" last="Roy">Rene Roy</name></author><author><name sortKey="Qin, Dujie" sort="Qin, Dujie" uniqKey="Qin D" first="Dujie" last="Qin">Dujie Qin</name></author><author><name sortKey="Yin, Rui" sort="Yin, Rui" uniqKey="Yin R" first="Rui" last="Yin">Rui Yin</name></author><author><name sortKey="Piehler, Lars T" sort="Piehler, Lars T" uniqKey="Piehler L" first="Lars T." last="Piehler">Lars T. Piehler</name></author><author><name sortKey="Esfand, Roseita" sort="Esfand, Roseita" uniqKey="Esfand R" first="Roseita" last="Esfand">Roseita Esfand</name></author><author><name sortKey="Tomalia, Donald A" sort="Tomalia, Donald A" uniqKey="Tomalia D" first="Donald A." last="Tomalia">Donald A. Tomalia</name></author><author><name sortKey="Baker, James R" sort="Baker, James R" uniqKey="Baker J" first="James R." last="Baker">James R. Baker</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:5B1815B5585E4AAEDFF2060DF62E768E50583B6F</idno><date when="1999" year="1999">1999</date><idno type="doi">10.1021/bc980099n</idno><idno type="url">https://api.istex.fr/ark:/67375/TPS-5BZ0PS4B-4/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000051</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000051</idno><idno type="wicri:Area/Istex/Curation">000051</idno><idno type="wicri:Area/Istex/Checkpoint">000794</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000794</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Inhibition of Viral Adhesion and Infection by Sialic-Acid-Conjugated
Dendritic Polymers</title><author><name sortKey="Reuter, Jon D" sort="Reuter, Jon D" uniqKey="Reuter J" first="Jon D." last="Reuter">Jon D. Reuter</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation><affiliation></affiliation><affiliation></affiliation></author><author><name sortKey="Myc, Andrzej" sort="Myc, Andrzej" uniqKey="Myc A" first="Andrzej" last="Myc">Andrzej Myc</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Hayes, Michael M" sort="Hayes, Michael M" uniqKey="Hayes M" first="Michael M." last="Hayes">Michael M. Hayes</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Gan, Zhonghong" sort="Gan, Zhonghong" uniqKey="Gan Z" first="Zhonghong" last="Gan">Zhonghong Gan</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Roy, Rene" sort="Roy, Rene" uniqKey="Roy R" first="Rene" last="Roy">Rene Roy</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Qin, Dujie" sort="Qin, Dujie" uniqKey="Qin D" first="Dujie" last="Qin">Dujie Qin</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation></author><author><name sortKey="Yin, Rui" sort="Yin, Rui" uniqKey="Yin R" first="Rui" last="Yin">Rui Yin</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation></author><author><name sortKey="Piehler, Lars T" sort="Piehler, Lars T" uniqKey="Piehler L" first="Lars T." last="Piehler">Lars T. Piehler</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation></author><author><name sortKey="Esfand, Roseita" sort="Esfand, Roseita" uniqKey="Esfand R" first="Roseita" last="Esfand">Roseita Esfand</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation></author><author><name sortKey="Tomalia, Donald A" sort="Tomalia, Donald A" uniqKey="Tomalia D" first="Donald A." last="Tomalia">Donald A. Tomalia</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation></author><author><name sortKey="Baker, James R" sort="Baker, James R" uniqKey="Baker J" first="James R." last="Baker">James R. Baker</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Center for Biologic Nanotechnology, Department of Internal Medicine, Division of Allergy, 1150 West MedicalCenter Drive, Room 9220 MSRB III, University of Michigan, Unit for Laboratory Animal Medicine, University ofMichigan, Ann Arbor, Michigan 48109, Department of Chemistry, University of Ottawa, Canada, and MichiganMolecular Institute, Midland</wicri:cityArea></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Bioconjugate Chemistry</title><title level="j" type="abbrev">Bioconjugate Chem.</title><idno type="ISSN">1043-1802</idno><idno type="eISSN">1520-4812</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published" when="1999-02-24">1999</date><date when="1999-03-15">1999</date><biblScope unit="vol">10</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="271">271</biblScope><biblScope unit="page" to="278">278</biblScope></imprint><idno type="ISSN">1043-1802</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1043-1802</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Multiple sialic acid (SA) residues conjugated to a linear polyacrylamide backbone are more effective than monomeric SA at inhibiting influenza-induced agglutination of red blood cells. However, “polymeric inhibitors” based on polyacrylamide backbones are cytotoxic. Dendritic polymers offer a nontoxic alternative to polyacrylamide and may provide a variety of potential synthetic inhibitors of influenza virus adhesion due to the wide range of available polymer structures. We evaluated several dendritic polymeric inhibitors, including spheroidal, linear, linear-dendron copolymers, comb-branched, and dendrigraft polymers, for the ability to inhibit virus hemagglutination (HA) and to block infection of mammalian cells in vitro. Four viruses were tested: influenza A H2N2 (selectively propagated two ways), X-31 influenza A H3N2, and sendai. The most potent of the linear and spheroidal inhibitors were 32−256-fold more effective than monomeric SA at inhibiting HA by the H2N2 influenza virus. Linear-dendron copolymers were 1025−8200-fold more effective against H2N2 influenza, X-31 influenza, and sendai viruses. The most effective were the comb-branched and dendrigraft inhibitors, which showed up to 50000-fold increased activity against these viruses. We were able to demonstrate significant (p < 0.001) dose-dependent reduction of influenza infection in mammalian cells by polymeric inhibitors, the first such demonstration for multivalent SA inhibitors. Effective dendrimer polymers were not cytotoxic to mammalian cells at therapeutic levels. Of additional interest, variation in the inhibitory effect was observed with different viruses, suggesting possible differences due to specific growth conditions of virus. SA-conjugated dendritic polymers may provide a new therapeutic modality for viruses that employ SA as their target receptor.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Michigan</li></region></list><tree><country name="États-Unis"><region name="Michigan"><name sortKey="Reuter, Jon D" sort="Reuter, Jon D" uniqKey="Reuter J" first="Jon D." last="Reuter">Jon D. Reuter</name></region><name sortKey="Baker, James R" sort="Baker, James R" uniqKey="Baker J" first="James R." last="Baker">James R. Baker</name><name sortKey="Baker, James R" sort="Baker, James R" uniqKey="Baker J" first="James R." last="Baker">James R. Baker</name><name sortKey="Esfand, Roseita" sort="Esfand, Roseita" uniqKey="Esfand R" first="Roseita" last="Esfand">Roseita Esfand</name><name sortKey="Gan, Zhonghong" sort="Gan, Zhonghong" uniqKey="Gan Z" first="Zhonghong" last="Gan">Zhonghong Gan</name><name sortKey="Hayes, Michael M" sort="Hayes, Michael M" uniqKey="Hayes M" first="Michael M." last="Hayes">Michael M. Hayes</name><name sortKey="Myc, Andrzej" sort="Myc, Andrzej" uniqKey="Myc A" first="Andrzej" last="Myc">Andrzej Myc</name><name sortKey="Piehler, Lars T" sort="Piehler, Lars T" uniqKey="Piehler L" first="Lars T." last="Piehler">Lars T. Piehler</name><name sortKey="Qin, Dujie" sort="Qin, Dujie" uniqKey="Qin D" first="Dujie" last="Qin">Dujie Qin</name><name sortKey="Roy, Rene" sort="Roy, Rene" uniqKey="Roy R" first="Rene" last="Roy">Rene Roy</name><name sortKey="Tomalia, Donald A" sort="Tomalia, Donald A" uniqKey="Tomalia D" first="Donald A." last="Tomalia">Donald A. Tomalia</name><name sortKey="Yin, Rui" sort="Yin, Rui" uniqKey="Yin R" first="Rui" last="Yin">Rui Yin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/Istex/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000794 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Checkpoint/biblio.hfd -nk 000794 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= Istex
|étape= Checkpoint
|type= RBID
|clé= ISTEX:5B1815B5585E4AAEDFF2060DF62E768E50583B6F
|texte= Inhibition of Viral Adhesion and Infection by Sialic-Acid-Conjugated Dendritic Polymers
}}
| This area was generated with Dilib version V0.6.33. |  |