Citation: Guo Ye, Fu Lili, Fan Xiaowen, Shi Xuanling. Stapled SC34EK fusion inhibitors with high potency against HIV-1 and improved protease resistance[J]. Chinese Chemical Letters, ;2018, 29(7): 1167-1170. doi: 10.1016/j.cclet.2018.03.024 shu

Stapled SC34EK fusion inhibitors with high potency against HIV-1 and improved protease resistance

Guo Ye ^a ,
Fu Lili ^b ,
Fan Xiaowen ^a ,
Shi Xuanling ^b,,

a.
School of Pharmacy, Baotou Medical College, Baotou 014060, China
b.
Comprehensive AIDS Research Center, School of Medicine, Tsinghua University, Beijing 100084, China

Corresponding author: Shi Xuanling, shixuanlingsk@mail.tsinghua.edu.cn
Received Date: 9 February 2018
Revised Date: 5 March 2018
Accepted Date: 19 March 2018
Available Online: 21 July 2018

Figures(3)

HIV fusion inhibitors are promising therapeutic agents for AIDS treatment. One fusion inhibitor has been approved as anti-HIV drug, while more of them are in preclinical studies or clinical trials. Highly active fusion inhibitors with excellent pharmacokinetic properties are still needed for development of anti-HIV drugs. We found that all-hydrocarbon staples inserted in SC34EK could not only enhance the inhibitory activity of inhibitors against HIV-1, but also improve protease resistance. Further study revealed that SC34EK-1 containing a staple was a potent fusion inhibitor with IC₅₀ value of 0.04-6.4 nmol/L towards diverse HIV-1 subtypes and half-life value of 112 min against protease hydrolysis. X-ray crystallography studies indicated that introduction of a hydrocarbon staple in SC34EK could make the amino acid at the interaction surface form perfect conformation to promote inhibitor peptide interacting with target.
- Fusion inhibitor,
- HIV-1,
- Stapled peptide,
- SC34EK
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