A theoretical investigation on the interaction of a new gene vector with DNA

摘要

A new neutral gene vector, based on a lipopolythiourea N-(2-(3-[2-(2-(3-[2-(3-methyl-thioueido)-ethyl] -thioureido)-ethylamino)-ethyl]-thioureido)-ethyl)- N′, N′- ditetradecyl-succinamide (DTTU) has recently been synthetized but its behavior is difficult to study at the experimental level. Density functional theory (DFT) calculations have thus been performed to predict its interaction mode with B-DNA. Its acidic properties are first computed and suggest that DTTU should be non-charged when interacting with DNA. Different ways of DTTU/DNA associations based on hydrogen bonding–namely external and groove-binding interactions—are then investigated. Our calculations clearly point out that external interaction is preferred with respect to groove-binding, due to three bifurcated hydrogen bonds between DTTU thiourea groups and DNA phosphates. Such results can be explained by the absence of charged groups in groove-binding whereas the negative charge of DNA phosphates deeply strengthens hydrogen bonds.