Synthesis, Biophysical Characterization, and Anti-HIV-1 Fusion Activity of DNA Quadruplex-based Inhibitors with Dipeptide MT Hook Conjugation.

Background: Human immunodeficiency virus type-1 (HIV-1) infection is the reason for the epidemic of acquired immunodeficiency syndrome (AIDS). The development of HIV-1 fusion inhibitors has gained increasing attention as they were found to be effective in the early stage of HIV-1. DNA G-quadruplex-based inhibitors have been found to interact with HIV-1 envelope glycoprotein, showing anti-HIV-1 fusion activity.

DNA Quadruplex-Based Inhibitor With Flexible Fragments at the 3' Terminal Shows Enhanced Anti-HIV-1 Fusion Activity.

Chemically optimizing the molecular structure of aptamers may enhance properties such as biological activity or metabolic stability. DNA quadruplex-based HIV-1 fusion inhibitors were found to interact with HIV-1 surface glycoprotein in aptamer mode. In this work, a series of quadruplex-based HIV-1 fusion inhibitors with flexible oligodeoxynucleotide fragments at the 3' terminal was discovered.

A novel multivalent DNA helix-based inhibitor showed enhanced anti-HIV-1 fusion activity.

DNA helix-based HIV-1 fusion inhibitors have been discovered as potent drug candidates, but further research is required to enhance their efficiency. The trimeric structure of the HIV-1 envelope glycoprotein provides a structural basis for multivalent drug design. In this work, a "multi-domain" strategy was adopted for design of an oligodeoxynucleotide with assembly, linkage, and activity domains.