Inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic polymers.
Identifieur interne : 000613 ( PubMed/Checkpoint ); précédent : 000612; suivant : 000614Inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic polymers.
Auteurs : J D Reuter [États-Unis] ; A. Myc ; M M Hayes ; Z. Gan ; R. Roy ; D. Qin ; R. Yin ; L T Piehler ; R. Esfand ; D A Tomalia ; J R BakerSource :
- Bioconjugate chemistry [ 1043-1802 ]
Descripteurs français
- KwdFr :
- Acides sialiques (pharmacologie), Acides sialiques (synthèse chimique), Adhérence cellulaire (), Animaux, Anticorps antiviraux, Embryon de poulet, Furets, Glycoconjugués (pharmacologie), Glycoconjugués (synthèse chimique), Poulets, Résines acryliques (), Résines acryliques (pharmacologie), Résines acryliques (synthèse chimique), Souris, Tests d'inhibition de l'hémagglutination, Virus de la grippe A (), Virus de la grippe A (immunologie), Virus de la grippe A (physiologie), Érythrocytes (virologie).
- MESH :
- immunologie : Virus de la grippe A.
- pharmacologie : Acides sialiques, Glycoconjugués, Résines acryliques.
- physiologie : Virus de la grippe A.
- synthèse chimique : Acides sialiques, Glycoconjugués, Résines acryliques.
- virologie : Érythrocytes.
- Adhérence cellulaire, Animaux, Anticorps antiviraux, Embryon de poulet, Furets, Poulets, Résines acryliques, Souris, Tests d'inhibition de l'hémagglutination, Virus de la grippe A.
English descriptors
- KwdEn :
- Acrylic Resins (chemical synthesis), Acrylic Resins (chemistry), Acrylic Resins (pharmacology), Animals, Antibodies, Viral, Cell Adhesion (drug effects), Chick Embryo, Chickens, Erythrocytes (virology), Ferrets, Glycoconjugates (chemical synthesis), Glycoconjugates (pharmacology), Hemagglutination Inhibition Tests, Influenza A virus (drug effects), Influenza A virus (immunology), Influenza A virus (physiology), Mice, Sialic Acids (chemical synthesis), Sialic Acids (pharmacology).
- MESH :
- chemical , chemical synthesis : Acrylic Resins, Glycoconjugates, Sialic Acids.
- chemical , chemistry : Acrylic Resins.
- chemical , pharmacology : Acrylic Resins, Glycoconjugates, Sialic Acids.
- drug effects : Cell Adhesion, Influenza A virus.
- immunology : Influenza A virus.
- physiology : Influenza A virus.
- virology : Erythrocytes.
- Animals, Antibodies, Viral, Chick Embryo, Chickens, Ferrets, Hemagglutination Inhibition Tests, Mice.
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.
DOI: 10.1021/bc980099n
PubMed: 10077477
Affiliations:
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pubmed:10077477Le document en format XML
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Myc</name></author><author><name sortKey="Hayes, M M" sort="Hayes, M M" uniqKey="Hayes M" first="M M" last="Hayes">M M Hayes</name></author><author><name sortKey="Gan, Z" sort="Gan, Z" uniqKey="Gan Z" first="Z" last="Gan">Z. Gan</name></author><author><name sortKey="Roy, R" sort="Roy, R" uniqKey="Roy R" first="R" last="Roy">R. Roy</name></author><author><name sortKey="Qin, D" sort="Qin, D" uniqKey="Qin D" first="D" last="Qin">D. Qin</name></author><author><name sortKey="Yin, R" sort="Yin, R" uniqKey="Yin R" first="R" last="Yin">R. Yin</name></author><author><name sortKey="Piehler, L T" sort="Piehler, L T" uniqKey="Piehler L" first="L T" last="Piehler">L T Piehler</name></author><author><name sortKey="Esfand, R" sort="Esfand, R" uniqKey="Esfand R" first="R" last="Esfand">R. 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Esfand</name></author><author><name sortKey="Tomalia, D A" sort="Tomalia, D A" uniqKey="Tomalia D" first="D A" last="Tomalia">D A Tomalia</name></author><author><name sortKey="Baker, J R" sort="Baker, J R" uniqKey="Baker J" first="J R" last="Baker">J R Baker</name></author></analytic><series><title level="j">Bioconjugate chemistry</title><idno type="ISSN">1043-1802</idno></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acrylic Resins (chemical synthesis)</term><term>Acrylic Resins (chemistry)</term><term>Acrylic Resins (pharmacology)</term><term>Animals</term><term>Antibodies, Viral</term><term>Cell Adhesion (drug effects)</term><term>Chick Embryo</term><term>Chickens</term><term>Erythrocytes (virology)</term><term>Ferrets</term><term>Glycoconjugates (chemical synthesis)</term><term>Glycoconjugates (pharmacology)</term><term>Hemagglutination Inhibition Tests</term><term>Influenza A virus (drug effects)</term><term>Influenza A virus (immunology)</term><term>Influenza A virus (physiology)</term><term>Mice</term><term>Sialic Acids (chemical synthesis)</term><term>Sialic Acids (pharmacology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acides sialiques (pharmacologie)</term><term>Acides sialiques (synthèse chimique)</term><term>Adhérence cellulaire ()</term><term>Animaux</term><term>Anticorps antiviraux</term><term>Embryon de poulet</term><term>Furets</term><term>Glycoconjugués (pharmacologie)</term><term>Glycoconjugués (synthèse chimique)</term><term>Poulets</term><term>Résines acryliques ()</term><term>Résines acryliques (pharmacologie)</term><term>Résines acryliques (synthèse chimique)</term><term>Souris</term><term>Tests d'inhibition de l'hémagglutination</term><term>Virus de la grippe A ()</term><term>Virus de la grippe A (immunologie)</term><term>Virus de la grippe A (physiologie)</term><term>Érythrocytes (virologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Acrylic Resins</term><term>Glycoconjugates</term><term>Sialic Acids</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Acrylic Resins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Acrylic Resins</term><term>Glycoconjugates</term><term>Sialic Acids</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Adhesion</term><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acides sialiques</term><term>Glycoconjugués</term><term>Résines acryliques</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Acides sialiques</term><term>Glycoconjugués</term><term>Résines acryliques</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Érythrocytes</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Erythrocytes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Antibodies, Viral</term><term>Chick Embryo</term><term>Chickens</term><term>Ferrets</term><term>Hemagglutination Inhibition Tests</term><term>Mice</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adhérence cellulaire</term><term>Animaux</term><term>Anticorps antiviraux</term><term>Embryon de poulet</term><term>Furets</term><term>Poulets</term><term>Résines acryliques</term><term>Souris</term><term>Tests d'inhibition de l'hémagglutination</term><term>Virus de la grippe A</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">10077477</PMID><DateCompleted><Year>1999</Year><Month>04</Month><Day>29</Day></DateCompleted><DateRevised><Year>2007</Year><Month>11</Month><Day>14</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1043-1802</ISSN><JournalIssue CitedMedium="Print"><Volume>10</Volume><Issue>2</Issue><PubDate><MedlineDate>1999 Mar-Apr</MedlineDate></PubDate></JournalIssue><Title>Bioconjugate chemistry</Title><ISOAbbreviation>Bioconjug. Chem.</ISOAbbreviation></Journal><ArticleTitle>Inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic polymers.</ArticleTitle><Pagination><MedlinePgn>271-8</MedlinePgn></Pagination><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Reuter</LastName><ForeName>J D</ForeName><Initials>JD</Initials><AffiliationInfo><Affiliation>Center for Biologic Nanotechnology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Myc</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Hayes</LastName><ForeName>M M</ForeName><Initials>MM</Initials></Author><Author ValidYN="Y"><LastName>Gan</LastName><ForeName>Z</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Roy</LastName><ForeName>R</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Qin</LastName><ForeName>D</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Yin</LastName><ForeName>R</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Piehler</LastName><ForeName>L T</ForeName><Initials>LT</Initials></Author><Author ValidYN="Y"><LastName>Esfand</LastName><ForeName>R</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Tomalia</LastName><ForeName>D A</ForeName><Initials>DA</Initials></Author><Author ValidYN="Y"><LastName>Baker</LastName><ForeName>J R</ForeName><Initials>JR</Initials><Suffix>Jr</Suffix></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>RR0 7008-21</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Bioconjug Chem</MedlineTA><NlmUniqueID>9010319</NlmUniqueID><ISSNLinking>1043-1802</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000180">Acrylic Resins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D006001">Glycoconjugates</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012794">Sialic Acids</NameOfSubstance></Chemical><Chemical><RegistryNumber>9003-05-8</RegistryNumber><NameOfSubstance UI="C016679">polyacrylamide</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000180" MajorTopicYN="N">Acrylic Resins</DescriptorName><QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002448" MajorTopicYN="N">Cell Adhesion</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002642" MajorTopicYN="N">Chick Embryo</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002645" MajorTopicYN="N">Chickens</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004912" MajorTopicYN="N">Erythrocytes</DescriptorName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005289" MajorTopicYN="N">Ferrets</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006001" MajorTopicYN="N">Glycoconjugates</DescriptorName><QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006385" MajorTopicYN="N">Hemagglutination Inhibition Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009980" MajorTopicYN="N">Influenza A virus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012794" MajorTopicYN="N">Sialic Acids</DescriptorName><QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1999</Year><Month>3</Month><Day>17</Day><Hour>3</Hour><Minute>4</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>3</Month><Day>28</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1999</Year><Month>3</Month><Day>17</Day><Hour>3</Hour><Minute>4</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10077477</ArticleId><ArticleId IdType="doi">10.1021/bc980099n</ArticleId><ArticleId IdType="pii">bc980099n</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Baker, J R" sort="Baker, J R" uniqKey="Baker J" first="J R" last="Baker">J R Baker</name><name sortKey="Esfand, R" sort="Esfand, R" uniqKey="Esfand R" first="R" last="Esfand">R. Esfand</name><name sortKey="Gan, Z" sort="Gan, Z" uniqKey="Gan Z" first="Z" last="Gan">Z. Gan</name><name sortKey="Hayes, M M" sort="Hayes, M M" uniqKey="Hayes M" first="M M" last="Hayes">M M Hayes</name><name sortKey="Myc, A" sort="Myc, A" uniqKey="Myc A" first="A" last="Myc">A. Myc</name><name sortKey="Piehler, L T" sort="Piehler, L T" uniqKey="Piehler L" first="L T" last="Piehler">L T Piehler</name><name sortKey="Qin, D" sort="Qin, D" uniqKey="Qin D" first="D" last="Qin">D. Qin</name><name sortKey="Roy, R" sort="Roy, R" uniqKey="Roy R" first="R" last="Roy">R. Roy</name><name sortKey="Tomalia, D A" sort="Tomalia, D A" uniqKey="Tomalia D" first="D A" last="Tomalia">D A Tomalia</name><name sortKey="Yin, R" sort="Yin, R" uniqKey="Yin R" first="R" last="Yin">R. Yin</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Reuter, J D" sort="Reuter, J D" uniqKey="Reuter J" first="J D" last="Reuter">J D Reuter</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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