Stapled SC34EK fusion inhibitors with high potency against HIV-1 and improved protease resistance
| Autor: | Ye Guo, Xiao-Wen Fan, Lili Fu, Xuanling Shi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Drug Fusion Protease media_common.quotation_subject medicine.medical_treatment Peptide General Chemistry Pharmacology 010402 general chemistry 01 natural sciences 0104 chemical sciences Amino acid 03 medical and health sciences 030104 developmental biology chemistry Pharmacokinetics medicine Potency IC50 media_common |
| Zdroj: | Chinese Chemical Letters. 29:1167-1170 |
| ISSN: | 1001-8417 |
| DOI: | 10.1016/j.cclet.2018.03.024 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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