The improved efficacy of Sifuvirtide compared with enfuvirtide might be related to its selectivity for the rigid biomembrane, as determined through surface plasmon resonance
Most mechanistic studies on human immunodeficiency virus (HIV) peptide fusion inhibitors have focused on the interactions between fusion inhibitors and viral envelope proteins. However, the interactions of fusion inhibitors with viral membranes are also essential for the efficacy of these drugs. Her...
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| description | Most mechanistic studies on human immunodeficiency virus (HIV) peptide fusion inhibitors have focused on the interactions between fusion inhibitors and viral envelope proteins. However, the interactions of fusion inhibitors with viral membranes are also essential for the efficacy of these drugs. Here, we utilized surface plasmon resonance (SPR) technology to study the interactions between the HIV fusion inhibitor peptides sifuvirtide and enfuvirtide and biomembrane models. Sifuvirtide presented selectivity toward biomembrane models composed of saturated dipalmitoylphosphatidylcholine (DPPC) (32-fold higher compared with unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [POPC]) and sphingomyelin (SM) (31-fold higher compared with POPC), which are rigid compositions enriched in the HIV viral membrane. In contrast, enfuvirtide showed no significant selectively toward these rigid membrane models. Furthermore, the bindings of sifuvirtide and enfuvirtide to SM bilayers were markedly higher than those to monolayers (14-fold and 23-fold, respectively), indicating that the inner leaflet influences the binding of these drugs to SM bilayers. No obvious differences were noted in the bindings of either peptide to the other mono- and bilayer models tested, illustrating that both peptides interact with these membranes through surface-binding. The bindings of the inhibitor peptides to biomembranes were found to be driven predominantly by hydrophobic interactions rather than electrostatic interactions, as determined by comparing their affinities to those of positively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (EPC) to zwitterionic membrane models. The improved efficiency of sifuvirtide relative to enfuvirtide might be related to its ability to adsorb on rigid lipidic areas, such as the viral envelope and lipid rafts, which results in an increased sifuvirtide concentration at the fusion site. |
| doi_str_mv | 10.1371/journal.pone.0171567 |
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However, the interactions of fusion inhibitors with viral membranes are also essential for the efficacy of these drugs. Here, we utilized surface plasmon resonance (SPR) technology to study the interactions between the HIV fusion inhibitor peptides sifuvirtide and enfuvirtide and biomembrane models. Sifuvirtide presented selectivity toward biomembrane models composed of saturated dipalmitoylphosphatidylcholine (DPPC) (32-fold higher compared with unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [POPC]) and sphingomyelin (SM) (31-fold higher compared with POPC), which are rigid compositions enriched in the HIV viral membrane. In contrast, enfuvirtide showed no significant selectively toward these rigid membrane models. Furthermore, the bindings of sifuvirtide and enfuvirtide to SM bilayers were markedly higher than those to monolayers (14-fold and 23-fold, respectively), indicating that the inner leaflet influences the binding of these drugs to SM bilayers. No obvious differences were noted in the bindings of either peptide to the other mono- and bilayer models tested, illustrating that both peptides interact with these membranes through surface-binding. The bindings of the inhibitor peptides to biomembranes were found to be driven predominantly by hydrophobic interactions rather than electrostatic interactions, as determined by comparing their affinities to those of positively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (EPC) to zwitterionic membrane models. The improved efficiency of sifuvirtide relative to enfuvirtide might be related to its ability to adsorb on rigid lipidic areas, such as the viral envelope and lipid rafts, which results in an increased sifuvirtide concentration at the fusion site.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0171567</identifier><identifier>PMID: 28207776</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antiretroviral drugs ; Binding ; Biochemistry ; Biology and Life Sciences ; Biosensors ; Dipalmitoyl phosphatidylcholine ; Dipalmitoylphosphatidylcholine ; Drugs ; Electrostatic properties ; Enfuvirtide ; Epidemiology ; Hematology ; HIV ; HIV Envelope Protein gp41 - chemistry ; HIV Envelope Protein gp41 - pharmacology ; HIV Fusion Inhibitors - chemistry ; HIV Fusion Inhibitors - pharmacology ; Human immunodeficiency virus ; Humans ; Hydrophobicity ; Inhibitors ; Laboratories ; Lipid Bilayers - chemistry ; Lipid rafts ; Lipids ; Medicine and Health Sciences ; Membranes ; Metabolism ; Peptide Fragments - chemistry ; Peptide Fragments - pharmacology ; Peptides ; Peptides - chemistry ; Peptides - pharmacology ; Pharmacology ; Phosphocholine ; Phosphocreatine ; Proteins ; Rafts ; Resonance ; Selectivity ; Sensors ; Sphingomyelin ; Surface plasmon resonance ; Surface Plasmon Resonance - methods ; Toxicology ; Viral envelopes ; Viral infections ; Viruses</subject><ispartof>PloS one, 2017-02, Vol.12 (2), p.e0171567</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2017 Cao et al 2017 Cao et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-bb8eaac52b8ce0290420e9e6ad4f74c51ee174bd0f287d68996db9e31b21e9933</citedby><cites>FETCH-LOGICAL-c725t-bb8eaac52b8ce0290420e9e6ad4f74c51ee174bd0f287d68996db9e31b21e9933</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/PMC5312942/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312942/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28207776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Jiang, Shibo</contributor><creatorcontrib>Cao, Ping</creatorcontrib><creatorcontrib>Dou, Guifang</creatorcontrib><creatorcontrib>Cheng, Yuanguo</creatorcontrib><creatorcontrib>Che, Jinjing</creatorcontrib><title>The improved efficacy of Sifuvirtide compared with enfuvirtide might be related to its selectivity for the rigid biomembrane, as determined through surface plasmon resonance</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Most mechanistic studies on human immunodeficiency virus (HIV) peptide fusion inhibitors have focused on the interactions between fusion inhibitors and viral envelope proteins. However, the interactions of fusion inhibitors with viral membranes are also essential for the efficacy of these drugs. Here, we utilized surface plasmon resonance (SPR) technology to study the interactions between the HIV fusion inhibitor peptides sifuvirtide and enfuvirtide and biomembrane models. Sifuvirtide presented selectivity toward biomembrane models composed of saturated dipalmitoylphosphatidylcholine (DPPC) (32-fold higher compared with unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [POPC]) and sphingomyelin (SM) (31-fold higher compared with POPC), which are rigid compositions enriched in the HIV viral membrane. In contrast, enfuvirtide showed no significant selectively toward these rigid membrane models. Furthermore, the bindings of sifuvirtide and enfuvirtide to SM bilayers were markedly higher than those to monolayers (14-fold and 23-fold, respectively), indicating that the inner leaflet influences the binding of these drugs to SM bilayers. No obvious differences were noted in the bindings of either peptide to the other mono- and bilayer models tested, illustrating that both peptides interact with these membranes through surface-binding. The bindings of the inhibitor peptides to biomembranes were found to be driven predominantly by hydrophobic interactions rather than electrostatic interactions, as determined by comparing their affinities to those of positively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (EPC) to zwitterionic membrane models. The improved efficiency of sifuvirtide relative to enfuvirtide might be related to its ability to adsorb on rigid lipidic areas, such as the viral envelope and lipid rafts, which results in an increased sifuvirtide concentration at the fusion site.</description><subject>Analysis</subject><subject>Antiretroviral drugs</subject><subject>Binding</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Biosensors</subject><subject>Dipalmitoyl phosphatidylcholine</subject><subject>Dipalmitoylphosphatidylcholine</subject><subject>Drugs</subject><subject>Electrostatic properties</subject><subject>Enfuvirtide</subject><subject>Epidemiology</subject><subject>Hematology</subject><subject>HIV</subject><subject>HIV Envelope Protein gp41 - chemistry</subject><subject>HIV Envelope Protein gp41 - pharmacology</subject><subject>HIV Fusion Inhibitors - chemistry</subject><subject>HIV Fusion Inhibitors - pharmacology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Hydrophobicity</subject><subject>Inhibitors</subject><subject>Laboratories</subject><subject>Lipid Bilayers - 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No obvious differences were noted in the bindings of either peptide to the other mono- and bilayer models tested, illustrating that both peptides interact with these membranes through surface-binding. The bindings of the inhibitor peptides to biomembranes were found to be driven predominantly by hydrophobic interactions rather than electrostatic interactions, as determined by comparing their affinities to those of positively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (EPC) to zwitterionic membrane models. The improved efficiency of sifuvirtide relative to enfuvirtide might be related to its ability to adsorb on rigid lipidic areas, such as the viral envelope and lipid rafts, which results in an increased sifuvirtide concentration at the fusion site.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28207776</pmid><doi>10.1371/journal.pone.0171567</doi><tpages>e0171567</tpages><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; PubMed Central; EZB Electronic Journals Library |
| subjects | Analysis Antiretroviral drugs Binding Biochemistry Biology and Life Sciences Biosensors Dipalmitoyl phosphatidylcholine Dipalmitoylphosphatidylcholine Drugs Electrostatic properties Enfuvirtide Epidemiology Hematology HIV HIV Envelope Protein gp41 - chemistry HIV Envelope Protein gp41 - pharmacology HIV Fusion Inhibitors - chemistry HIV Fusion Inhibitors - pharmacology Human immunodeficiency virus Humans Hydrophobicity Inhibitors Laboratories Lipid Bilayers - chemistry Lipid rafts Lipids Medicine and Health Sciences Membranes Metabolism Peptide Fragments - chemistry Peptide Fragments - pharmacology Peptides Peptides - chemistry Peptides - pharmacology Pharmacology Phosphocholine Phosphocreatine Proteins Rafts Resonance Selectivity Sensors Sphingomyelin Surface plasmon resonance Surface Plasmon Resonance - methods Toxicology Viral envelopes Viral infections Viruses |
| title | The improved efficacy of Sifuvirtide compared with enfuvirtide might be related to its selectivity for the rigid biomembrane, as determined through surface plasmon resonance |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T17%3A33%3A46IST&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=The%20improved%20efficacy%20of%20Sifuvirtide%20compared%20with%20enfuvirtide%20might%20be%20related%20to%20its%20selectivity%20for%20the%20rigid%20biomembrane,%20as%20determined%20through%20surface%20plasmon%20resonance&rft.jtitle=PloS%20one&rft.au=Cao,%20Ping&rft.date=2017-02-16&rft.volume=12&rft.issue=2&rft.spage=e0171567&rft.pages=e0171567-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0171567&rft_dat=%3Cgale_plos_%3EA481461471%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=1869029788&rft_id=info:pmid/28207776&rft_galeid=A481461471&rft_doaj_id=oai_doaj_org_article_37b3b35df50d43c4be79ca1c9b57210a&rfr_iscdi=true |