Grifonin-1: a small HIV-1 entry inhibitor derived from the algal lectin, Griffithsin
Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used t...
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| Veröffentlicht in: | PloS one 2010-12, Vol.5 (12), p.e14360 |
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| creator | Micewicz, Ewa D Cole, Amy L Jung, Chun-Ling Luong, Hai Phillips, Martin L Pratikhya, Pratikhya Sharma, Shantanu Waring, Alan J Cole, Alexander M Ruchala, Piotr |
| description | Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties.
The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC(50) of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface.
Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1. |
| doi_str_mv | 10.1371/journal.pone.0014360 |
| format | Article |
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The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC(50) of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface.
Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0014360</identifier><identifier>PMID: 21179548</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Algae ; Algal Proteins - chemistry ; Algorithms ; Amino Acid Sequence ; Amino acids ; Antiviral activity ; Antiviral agents ; Binding sites ; Biochemistry ; Biological activity ; Biopolymers ; Carbohydrates ; Chemical Biology/Small Molecule Chemistry ; Chemistry/Organic Chemistry ; Cloning ; Disulfides - chemistry ; Drug Design ; Glycoprotein gp120 ; Glycoprotein gp41 ; Glycoproteins ; Health aspects ; HIV ; HIV Core Protein p24 - chemistry ; HIV Fusion Inhibitors - pharmacology ; HIV Infections - prevention & control ; HIV-1 - metabolism ; Homology ; Human immunodeficiency virus ; Humans ; Hydrogen ; Hydrophobicity ; Infections ; Infectious Diseases/HIV Infection and AIDS ; Lectins ; Lectins - chemistry ; Mannose ; Medicine ; Molecular biology ; Molecular Sequence Data ; Monosaccharides ; N-glycans ; Oligomers ; Pattern recognition ; Peptides ; Peptides - chemistry ; Plant Proteins ; Polarity ; Polysaccharides ; Protein binding ; Protein Conformation ; Protein Structure, Secondary ; Proteins ; Rhodophyta - metabolism ; Sequence Homology, Amino Acid ; Simulation ; Solvents ; Toxicity ; Virology/Antivirals, including Modes of Action and Resistance ; Virology/New Therapies, including Antivirals and Immunotherapy ; Viruses</subject><ispartof>PloS one, 2010-12, Vol.5 (12), p.e14360</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Micewicz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Micewicz et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-80b3283a2d5512a5126f324fa51b16e5020ac497889302be12c96c2b53b282e83</citedby><cites>FETCH-LOGICAL-c691t-80b3283a2d5512a5126f324fa51b16e5020ac497889302be12c96c2b53b282e83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002932/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002932/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21179548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Stoddart, Cheryl A.</contributor><creatorcontrib>Micewicz, Ewa D</creatorcontrib><creatorcontrib>Cole, Amy L</creatorcontrib><creatorcontrib>Jung, Chun-Ling</creatorcontrib><creatorcontrib>Luong, Hai</creatorcontrib><creatorcontrib>Phillips, Martin L</creatorcontrib><creatorcontrib>Pratikhya, Pratikhya</creatorcontrib><creatorcontrib>Sharma, Shantanu</creatorcontrib><creatorcontrib>Waring, Alan J</creatorcontrib><creatorcontrib>Cole, Alexander M</creatorcontrib><creatorcontrib>Ruchala, Piotr</creatorcontrib><title>Grifonin-1: a small HIV-1 entry inhibitor derived from the algal lectin, Griffithsin</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties.
The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC(50) of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface.
Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1.</description><subject>Algae</subject><subject>Algal Proteins - chemistry</subject><subject>Algorithms</subject><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Antiviral activity</subject><subject>Antiviral agents</subject><subject>Binding sites</subject><subject>Biochemistry</subject><subject>Biological activity</subject><subject>Biopolymers</subject><subject>Carbohydrates</subject><subject>Chemical Biology/Small Molecule Chemistry</subject><subject>Chemistry/Organic Chemistry</subject><subject>Cloning</subject><subject>Disulfides - chemistry</subject><subject>Drug Design</subject><subject>Glycoprotein gp120</subject><subject>Glycoprotein gp41</subject><subject>Glycoproteins</subject><subject>Health aspects</subject><subject>HIV</subject><subject>HIV Core Protein p24 - chemistry</subject><subject>HIV Fusion Inhibitors - pharmacology</subject><subject>HIV Infections - prevention & control</subject><subject>HIV-1 - metabolism</subject><subject>Homology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Hydrogen</subject><subject>Hydrophobicity</subject><subject>Infections</subject><subject>Infectious Diseases/HIV Infection and AIDS</subject><subject>Lectins</subject><subject>Lectins - chemistry</subject><subject>Mannose</subject><subject>Medicine</subject><subject>Molecular biology</subject><subject>Molecular Sequence Data</subject><subject>Monosaccharides</subject><subject>N-glycans</subject><subject>Oligomers</subject><subject>Pattern recognition</subject><subject>Peptides</subject><subject>Peptides - chemistry</subject><subject>Plant Proteins</subject><subject>Polarity</subject><subject>Polysaccharides</subject><subject>Protein binding</subject><subject>Protein Conformation</subject><subject>Protein Structure, Secondary</subject><subject>Proteins</subject><subject>Rhodophyta - metabolism</subject><subject>Sequence Homology, Amino Acid</subject><subject>Simulation</subject><subject>Solvents</subject><subject>Toxicity</subject><subject>Virology/Antivirals, including Modes of Action and Resistance</subject><subject>Virology/New Therapies, including Antivirals and Immunotherapy</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNku9r1DAcxosobk7_A9GAIAj2zI82TX0hjKHbwWCgc29DmiZ3OdLkluSG--9NvW5cQUFCSEg-3yfJk6coXiO4QKRBnzZ-F5ywi613agEhqgiFT4pj1BJcUgzJ04P5UfEixg2ENWGUPi-OMEJNW1fsuLg-D0Z7Z1yJPgMB4iCsBRfLmxIB5VK4B8atTWeSD6BXwdypHujgB5DWCgi7EhZYJZNxH8EopE1aR-NeFs-0sFG9msaT4ue3r9dnF-Xl1fny7PSylLRFqWSwI5gRgfu6RljkTjXBlc6zDlFVQwyFrNqGsZZA3CmEZUsl7mrSYYYVIyfF273u1vrIJ0MiRwRhxFB-fSaWe6L3YsO3wQwi3HMvDP-z4MOKi5CMtIrrSte9RrpviKiwkh1kGNGW9qzNd5Oj1pfptF03qF6O_gg7E53vOLPmK3_HCYQ4_0QWeDcJBH-7UzH948oTlc1V3Djts5gcTJT8tGoIQ7Rq6kwt_kLl1qvByBwJbfL6rODDrCAzSf1KK7GLkS9_fP9_9upmzr4_YNdK2BwBb3fJeBfnYLUHZfAxBqUfnUOQj4l-cIOPieZTonPZm0PXH4seIkx-A1et7gs</recordid><startdate>20101216</startdate><enddate>20101216</enddate><creator>Micewicz, Ewa D</creator><creator>Cole, Amy L</creator><creator>Jung, Chun-Ling</creator><creator>Luong, Hai</creator><creator>Phillips, Martin L</creator><creator>Pratikhya, Pratikhya</creator><creator>Sharma, Shantanu</creator><creator>Waring, Alan J</creator><creator>Cole, Alexander M</creator><creator>Ruchala, Piotr</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20101216</creationdate><title>Grifonin-1: a small HIV-1 entry inhibitor derived from the algal lectin, Griffithsin</title><author>Micewicz, Ewa D ; Cole, Amy L ; Jung, Chun-Ling ; Luong, Hai ; Phillips, Martin L ; Pratikhya, Pratikhya ; Sharma, Shantanu ; Waring, Alan J ; Cole, Alexander M ; Ruchala, Piotr</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-80b3283a2d5512a5126f324fa51b16e5020ac497889302be12c96c2b53b282e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Algae</topic><topic>Algal Proteins - 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We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties.
The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC(50) of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface.
Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21179548</pmid><doi>10.1371/journal.pone.0014360</doi><tpages>e14360</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1312181193 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Algae Algal Proteins - chemistry Algorithms Amino Acid Sequence Amino acids Antiviral activity Antiviral agents Binding sites Biochemistry Biological activity Biopolymers Carbohydrates Chemical Biology/Small Molecule Chemistry Chemistry/Organic Chemistry Cloning Disulfides - chemistry Drug Design Glycoprotein gp120 Glycoprotein gp41 Glycoproteins Health aspects HIV HIV Core Protein p24 - chemistry HIV Fusion Inhibitors - pharmacology HIV Infections - prevention & control HIV-1 - metabolism Homology Human immunodeficiency virus Humans Hydrogen Hydrophobicity Infections Infectious Diseases/HIV Infection and AIDS Lectins Lectins - chemistry Mannose Medicine Molecular biology Molecular Sequence Data Monosaccharides N-glycans Oligomers Pattern recognition Peptides Peptides - chemistry Plant Proteins Polarity Polysaccharides Protein binding Protein Conformation Protein Structure, Secondary Proteins Rhodophyta - metabolism Sequence Homology, Amino Acid Simulation Solvents Toxicity Virology/Antivirals, including Modes of Action and Resistance Virology/New Therapies, including Antivirals and Immunotherapy Viruses |
| title | Grifonin-1: a small HIV-1 entry inhibitor derived from the algal lectin, Griffithsin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T20%3A39%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Grifonin-1:%20a%20small%20HIV-1%20entry%20inhibitor%20derived%20from%20the%20algal%20lectin,%20Griffithsin&rft.jtitle=PloS%20one&rft.au=Micewicz,%20Ewa%20D&rft.date=2010-12-16&rft.volume=5&rft.issue=12&rft.spage=e14360&rft.pages=e14360-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0014360&rft_dat=%3Cgale_plos_%3EA473816475%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1312181193&rft_id=info:pmid/21179548&rft_galeid=A473816475&rft_doaj_id=oai_doaj_org_article_f4f5df1fd73a42ecb0821696d892a5c3&rfr_iscdi=true |