| 论文题目: | Glycosylated Enfuvirtide: A Long-Lasting Glycopeptide with Potent Anti-HIV Activity |
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| 作者: | Cheng Shuihong Chang Xuesong, Wang Yan, George F Gao, Shao Yiming, Ma Liying, Li Xuebing*. |
| 联系作者: | |
| 刊物名称: | J Med Chem |
| 期: | 58 |
| 卷: | 3 |
| 页: | 1372-9 |
| 年份: | 2015 |
| 影响因子: | 5.504 |
| 论文下载: | |
| 摘要: | Many peptide-based therapeutics have short circulatory half-lives. We report here that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be dramatically improved by a chemical glycosylation approach. A set of glycosylated ENFs with varying glycosylation sites and glycan structures were synthesized. Among these, a sialic acid-introduced peptide (SL-ENF) demonstrated a 15-fold extended half-life in rats relative to ENF (T1/2: 23.1 vs 1.5 h), and its antiviral potency was comparable to that of ENF (EC50: 2 vs 3 nM). SL-ENF bound to a functional fragment of the HIV fusogenic protein gp41 and formed complexes with high affinity and alpha-helicity, revealing the mechanism behind its potent antiviral activity. Because it is widely accepted in biology that glycosylation protects proteins from denaturation and proteases, our approach may be useful for the development of novel protein and peptide drugs with enhanced pharmaceutical properties. |
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