Drug-Receptor Interaction of Peptidic HIV-1 Protease: Polar Effect-II

Abstract

Klopman described the chemical reaction of metal ions and base ions in term of softness, E ‡ n and E ‡ m, respectively. By simple modification of known methods, Singh et al. made it applicable for neutral Lewis acids (transition metal salts) and bases (organic molecules) and also extended its application to biological systems for site selectivity and to explain reaction mechanism (markovnikov and anti-markovnikov rule), ligand-receptor interaction of testosterones, estrogens and tetrahydroimidazobenzodiazepinone. In this study effective atomic softness E ‡ n(eff) and E ‡ m(eff), and their change ΔE ‡ nm have been used for site selectivity and polar interaction between 51 peptidic HIV-1 protease inhibitors and receptor amino acids. ΔE ‡ nm values derived from drug-receptor interaction show that when one moiety on receptor behaves as nucleophile (O of valine amino acid) at the same time maximum electrophilic site of the drug (C-atom of the maximum E ‡ n(eff) value) orient itself to come close the respective site and make maximum interaction, while when another moiety on receptor behaves as electrophilic site (C of isoleucine amino acid), at the same time maximum nucleophilic site of the drug (O-atom of the maximum E ‡ m(eff) value) also orient itself to come close the respective site and make maximum interaction.

Drug-Receptor Interaction of Peptidic HIV-1 Protease: Intermolecular Interaction-III

“…Here, fifty-one peptidic HIV-1-PRIs [1] and receptor proteins (scheme 1) are the study materials [1][2][3]. The sites of interaction on receptor proteins are amino acids.…”

“…Out of fifty-one compounds listed in Table 1, the eighteen compounds (compound no. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] have the parent skeleton of Figure 1 (first set that is A group), which has 25 sites. Out of remaining thirty-three, the seventeen compounds (compound no.…”

“…In our previous publications we have studied pharmacokinetics followed by drugreceptor interaction based on hydrophobic and polar effect [1][2][3]. Here, we have studied intermolecular interaction between drug and receptor's amino acids that strengthen the formation of enzyme-inhibitor (EI) complexes [4].…”