Quantum chemical modelling of reactivity and selectivity of 1, 2-dithiolanes towards retroviral and cellular zinc fingers

Abstract

Interactions of 1, 2-dithiolane species with zinc-containing sites, which mimic the zinc finger domains of retroviral and the cellular zinc finger proteins, have been investigated by quantum chemistry tools. According to the calculations, the immediate domains of zinc binding sites in the cellular and retroviral zinc fingers interact differently with such agents of the disulphide family. Thus, when approaching the model cellular-type domains, the molecules of 1, 2-dithiolanes experience considerable potential barriers along the reaction path. However, these species react practically barrier-less with the model retroviral-type domains at the correlated DFT level. The results of the quantum chemical modelling provide firm support to the selectivity of 1, 2-dithiolanes towards retroviral and cellular zinc fingers. This can be of great practical importance for the design of therapeutics that accomplish functional inactivation of the zinc fingers of the human immunodeficiency virus (HIV-I) retroviral type nucleocapsid protein NCp7.