{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T01:28:07Z","timestamp":1768267687374,"version":"3.49.0"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["81630090"],"award-info":[{"award-number":["81630090"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["81373456"],"award-info":[{"award-number":["81373456"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["81672019"],"award-info":[{"award-number":["81672019"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["8161101485"],"award-info":[{"award-number":["8161101485"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2016YFC1201000"],"award-info":[{"award-number":["2016YFC1201000"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2016YFC1200405"],"award-info":[{"award-number":["2016YFC1200405"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2016YFC1202901"],"award-info":[{"award-number":["2016YFC1202901"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2016YFC1000905"],"award-info":[{"award-number":["2016YFC1000905"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Goverment","award":["Sanming Project of Medicine"],"award-info":[{"award-number":["Sanming Project of Medicine"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Peptides derived from the C-terminal heptad repeat (CHR) of human immunodeficiency virus type 1 (HIV-1) envelope protein transmembrane subunit gp41, such as T20 (enfuvirtide), can bind to the N-terminal heptad repeat (NHR) of gp41 and block six-helix bundle (6-HB) formation, thus inhibiting HIV-1 fusion with the target cell. However, clinical application of T20 is limited because of its low potency and genetic barrier to resistance. HP23, the shortest CHR peptide, exhibits better anti-HIV-1 activity than T20, but the HIV-1 strains with E49K mutations in gp41 will become resistant to it. Here, we modified HP23 by extending its C-terminal sequence using six amino acid residues (E6) and adding IDL (Ile-Asp-Leu) to the C-terminus of E6, which is expected to bind to the shallow pocket in the gp41 NHR N-terminal region. The newly designed peptide, designated HP23-E6-IDL, was about 2- to 16-fold more potent than HP23 against a broad spectrum of HIV-1 strains and more than 12-fold more effective against HIV-1 mutants resistant to HP23. These findings suggest that addition of an anchor\u2013tail to the C-terminus of a CHR peptide will allow binding with the pocket in the gp41 NHR that may increase the peptide\u2019s antiviral efficacy and its genetic barrier to resistance.<\/jats:p>","DOI":"10.3390\/molecules22111996","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T11:35:45Z","timestamp":1511177745000},"page":"1996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Adding an Artificial Tail\u2014Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile"],"prefix":"10.3390","volume":"22","author":[{"given":"Shan","family":"Su","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH, School of Basic Medical Sciences &amp; Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenxuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH, School of Basic Medical Sciences &amp; Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Hua","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH, School of Basic Medical Sciences &amp; 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":"Key Laboratory of Reproduction Regulation of National Population and Family Planning Commission, The Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH, School of Basic Medical Sciences &amp; 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 &amp; Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China"},{"name":"Key Laboratory of Reproduction Regulation of National Population and Family Planning Commission, The Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Fudan University, Shanghai 200032, China"},{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2165\/00003495-199957030-00006","article-title":"Managing resistance to anti-HIV drugs: An important consideration for effective disease management","volume":"57","author":"Vandamme","year":"1999","journal-title":"Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1016\/j.bbamem.2012.07.020","article-title":"HIV-1 variants with a single-point mutation in the gp41 pocket region exhibiting different susceptibility to HIV fusion inhibitors with pocket-or membrane-binding domain","volume":"1818","author":"Lu","year":"2012","journal-title":"Biochim. Biophys. 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