Sulfotyrosine dipeptide: Synthesis and evaluation as HIV-entry inhibitor

Abstract

Human immunodeficiency virus type 1 (HIV-1) is responsible for the worldwide AIDS pandemic. Due to the lack of prophylactic HIV-1 vaccine, drug treatment of the infected patients becomes essential to reduce the viral load and to slow down progression of the disease. Because of drug resistance, finding new antiviral agents is necessary for AIDS drug therapies. The interaction of gp120 and co-receptor (CCR5/CXCR4) mediates the entry of HIV-1 into host cells, which has been increasingly exploited in recent years as the target for new antiviral agents. A conserved co-receptor binding site on gp120 that recognizes sulfotyrosine (sTyr) residues represents a structural target to design novel HIV entry inhibitors. In this work, we developed an efficient synthesis of sulfotyrosine dipeptide and evaluated it as an HIV-1 entry inhibitor.

Structural Study of a New HIV‐1 Entry Inhibitor and Interaction with the HIV‐1 Fusion Peptide in Dodecylphosphocholine Micelles

“…Antiviral agents that block the HIV‐1 entry (entry inhibitors) are considered as an effective class of drugs and have been increasingly exploited in recent years . At present, only two members have been clinically approved: Enfuvirtide (T20), a 36‐mer water‐soluble peptide derived from the C‐terminal heptad repeat region of gp41 and Maraviroc (MVC), [7 ] which binds to the CCR5 co‐receptor and inhibits HIV‐1 entry by blocking the gp120‐CCR5 interaction.…”