Effect of Dimerization and Tetramerization on the Potency of HIV-1 Integrase Inhibitory Peptides

摘要

HIV-1 integrase (IN) is essential for the HIV virus replication cycle. Furthermore, it is a key enzyme for the ability of HIV to infect non-dividing cells. The mechanism of IN enzymatic activity involves two steps: 3'-processing and strand transfer. In addition to reverse transcriptase and protease, IN is an attractive target for HIV antiviral chemotherapy. It has no counterpart in mammalian cells, therefore selective IN inhibitors should not produce any side effects. Many IN inhibitors have been reported to date, and some promising compounds are in clinical trials. However, no clinically useful drugs have yet been approved. Here we present results of our studies on the effect of dimerization and tetramerization (Fig. 1) on the IN inhibitory potency of peptides. For these studies, we used IN inhibitory peptide sequences discovered by us or published by others. These results may be helpful in the process of designing new IN inhibitory drugs.