{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T07:21:49Z","timestamp":1768288909787,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,21]],"date-time":"2019-03-21T00:00:00Z","timestamp":1553126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81630090"],"award-info":[{"award-number":["81630090"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672019"],"award-info":[{"award-number":["81672019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8161101485"],"award-info":[{"award-number":["8161101485"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701998"],"award-info":[{"award-number":["81701998"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703571"],"award-info":[{"award-number":["81703571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Enfuvirtide (T20) is the first U.S. FDA-approved HIV fusion inhibitor-based anti-HIV drug. Its clinical application is limited because of its low potency and short half-life. We previously reported that peptide HP23-E6-IDL, containing both N- and C-terminal anchor-tails, exhibited stronger potency and a better resistance profile than T20. Here we designed an analogous peptide, YIK, by introducing a mutation, T639I, and then a lipopeptide, YIK-C16, by adding palmitic acid (C16) at the C-terminus of YIK. We found that YIK-C16 was 4.4- and 3.6-fold more potent than HP23-E6-IDL and YIK against HIV-1IIIB infection and 13.3- and 10.5-fold more effective than HP23-E6-IDL and YIK against HIV-1Bal infection, respectively. Consistently, the ex vivo anti-HIV-1IIIB activity, as determined by the highest dilution-fold of the serum causing 50% inhibition of HIV-1 infection, of YIK-C16 in the sera of pretreated mice was remarkably higher than that of YIK or HP23-E6-IDL. The serum half-life (t1\/2 = 5.9 h) of YIK-C16 was also significantly longer than that of YIK (t1\/2 = 1.3 h) and HP23-E6-IDL (t1\/2 = 1.0 h). These results suggest that the lipopeptide YIK-C16 shows promise for further development as a new anti-HIV drug with improved anti-HIV-1 activity and a prolonged half-life.<\/jats:p>","DOI":"10.3390\/molecules24061134","type":"journal-article","created":{"date-parts":[[2019,3,21]],"date-time":"2019-03-21T12:28:01Z","timestamp":1553171281000},"page":"1134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A Peptide-Based HIV-1 Fusion Inhibitor with Two Tail-Anchors and Palmitic Acid Exhibits Substantially Improved In Vitro and Ex Vivo Anti-HIV-1 Activity and Prolonged In Vivo Half-Life"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0593-9968","authenticated-orcid":false,"given":"Shan","family":"Su","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China"},{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giselle","family":"Rasquinha","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanying","family":"Du","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihua","family":"Li","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2255-0391","authenticated-orcid":false,"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China"},{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"},{"name":"NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S0140-6736(05)78279-9","article-title":"Effect of HAART on natural history of AIDS-related opportunistic disorders","volume":"351","author":"Sepkowitz","year":"1998","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1006\/bbrc.1993.2078","article-title":"Inhibition of HIV-1 infection by a fusion domain binding peptide from the HIV-1 envelope glycoprotein GP41","volume":"195","author":"Jiang","year":"1993","journal-title":"Biochem. Biophys. Res. 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