Design of Artificial C-Peptides as Potential Anti-HIV-1 Inhibitors Based on 6-HB Formation Mechanism

恩夫韦肽 第41页 拟肽 生物化学 脂质双层融合 化学 合理设计 生物 遗传学 抗原 表位
作者
Hui Luo,Yan Zhao,Yuheng Ma,Guodong Liang,Lu Ga,Meng Zhao
出处
期刊:Protein and Peptide Letters [Bentham Science Publishers]
卷期号:31
标识
DOI:10.2174/0109298665312274240530060233
摘要

Background: The six-helix bundle (6-HB) is a core structure formed during the membrane fusion process of viruses with the Class I envelope proteins. Peptide inhibitors, including the marketed Enfuvirtide, blocking the membrane fusion to exert inhibitory activity were designed based on the heptads repeat interactions in 6-HB. However, the drawbacks of Enfuvirtide, such as drug resistance and short half-life in vivo, have been confirmed in clinical applications. Therefore, novel design strategies are pivotal in the development of next-generation peptide-based fusion inhibitors. Objective: The de novo design of α-helical peptides against MERS-CoV and IAVs has successfully expedited the development of fusion inhibitors. The reported sequences were completely nonhomologous with natural peptides, which can provide some inspirations for the antiviral design against other pathogenic viruses with class I fusion proteins. Here, we design a series of artificial C-peptides based on the similar mechanism of 6-HB formation and general rules of heptads repeat interaction. Methods: The inhibitory activity of peptides against HIV-1 was assessed by HIV-1 Env-mediated cell-cell fusion assays. Interaction between artificial C-peptides and target peptides was evaluated by circular dichroism, polyacrylamide gel electrophoresis, size-exclusion chromatography, and sedimentation velocity analysis. Molecular docking studies were performed by using Schrödinger molecular modelling software. Results: The best-performing artificial C-peptide, 1SR, was highly active against HIV-1 env-mediated cell-cell fusion. 1SR binds to the gp41 NHR region, assembling polymer to prevent endogenous 6-HB formation. result: Artificial C-peptides exhibit potential inhibitory activities against HIV-1 env-mediated cell-cell fusion. Artificial C-peptides spatial structures and their interactions with exogenous gp41 NHR peptide N36. The salt bridge between 1SR Glu16 or Glu24 and NHR Lys574 essential for blocking gp41 6-HB formation. Conclusion: We have found an artificial C-lipopeptide lead compound with inhibitory activity against HIV-1. Also, this paper enriched both N- and C-teminal heptads repeat interaction rules in 6-HB and provided an effective idea for next-generation peptide-based fusion inhibitors against HIV-1.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
科目三应助乐观紫采纳,获得10
刚刚
我是小短腿的妹妹完成签到,获得积分20
1秒前
lily完成签到,获得积分10
1秒前
感谢有你发布了新的文献求助10
3秒前
wh2740完成签到,获得积分10
4秒前
SHAO应助可乐冰淇淋采纳,获得30
7秒前
7秒前
脑洞疼应助JUdy采纳,获得10
9秒前
何白发布了新的文献求助10
9秒前
Lu发布了新的文献求助10
10秒前
hugdoggy完成签到,获得积分10
12秒前
12秒前
桃子发布了新的文献求助30
15秒前
16秒前
Liufgui给风之星的求助进行了留言
16秒前
17秒前
Lucas应助桔子采纳,获得30
19秒前
JUdy发布了新的文献求助10
22秒前
15858833895发布了新的文献求助10
23秒前
许晓蝶完成签到,获得积分10
23秒前
花花完成签到 ,获得积分10
23秒前
wayne完成签到 ,获得积分10
26秒前
26秒前
hua完成签到,获得积分10
27秒前
可乐冰淇淋完成签到,获得积分10
28秒前
28秒前
贝湾完成签到,获得积分10
29秒前
量子星尘发布了新的文献求助10
30秒前
31秒前
水中鱼发布了新的文献求助10
32秒前
lin完成签到,获得积分10
33秒前
陌予完成签到 ,获得积分10
33秒前
34秒前
Fengliguantou发布了新的文献求助20
34秒前
桔子发布了新的文献求助30
34秒前
萨日呼完成签到,获得积分10
34秒前
彭栋完成签到,获得积分10
38秒前
Lu发布了新的文献求助10
38秒前
38秒前
43秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989115
求助须知:如何正确求助?哪些是违规求助? 3531367
关于积分的说明 11253688
捐赠科研通 3269986
什么是DOI,文献DOI怎么找? 1804868
邀请新用户注册赠送积分活动 882078
科研通“疑难数据库(出版商)”最低求助积分说明 809105