Addition of artificial salt bridge by Ile646Lys mutation in gp41 coiled-coil domain regulates 6-helical bundle formation

作者：Zhao, Lei; Hu, Zhi-Wen; Tong, Pei; Chen, Yong-Xiang^*; Zhao, Yu-Fen; Li, Yan-Mei

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(9): 2727-2732.

DOI：10.1016/j.bmcl.2013.02.071

• Salt bridge
• Gp41
• 6-Helical bundle
• Fusion inhibitor

HIV entry is mediated by the envelope glycoproteins gp120 and gp41. The gp41 subunit contains several functional domains: the N-terminal heptad repeat (NHR) domains fold a triple stranded coiled-coil forming a meta-stable prefusion intermediate. C-terminal heptad repeat (CHR) subsequently folds onto the hydrophobic grooves of the NHR coiled-coil to form a stable 6-helix bundle, which juxtaposes the viral and cellular membranes for fusion. The C34 which has 34 amino acid residues is known as the core structure in CHR. A highly anti-HIV peptide inhibitor derived from C34 was designed. An artificial salt bridge was added in the 6-helical bundle by substitution of lysine for Ile646. With a cholesterol modification at C-terminal, the inhibitor containing I646K mutation represented higher anti-viral activity than C34-cholesterol combination without mutation.

• 出版日期2013-5-1
• 单位清华大学