Small-Molecule CD4-Mimics [electronic resource] : Structure-Based Optimization of HIV-1 Entry Inhibition

• Ngôn ngữ: eng
• Ký hiệu phân loại: 620.1 Engineering mechanics and materials
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016
• Mô tả vật lý: Size: p. 330-334 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261007
• Chủ đề: 1. 60 applied life sciences; 2. Cd4; 3. Entry inhibitor; 4. Gp120; 5. Hiv; 6. Protein?protein interactions; 7. Structure-based drug design; 8. Thermodynamics; 9. Viral inhibition; 10. X-ray crystallography

Tóm tắt

We report the optimization, based on computational, thermodynamic, and crystallographic data, of a series of small-molecule ligands of the Phe43 cavity of the envelope glycoprotein gp120 of human immunodeficiency virus (HIV) has been achieved. Importantly, biological evaluation revealed that the small-molecule CD4 mimics (4?7) inhibit HIV-1 entry into target cells with both significantly higher potency and neutralization breadth than previous congeners, while maintaining high selectivity for the target virus. Their binding mode was characterized via thermodynamic and crystallographic studies.