Modelling of copper(II) binding to pentapeptides related to atrial natriuretic factor using the 3χv connectivity index

Abstract

Using molecular graph theory we studied the binding of NSFRY-NH₂ and 12 related pentapeptide amides to Cu(II) as a model system for atrial natriuretic factor (ANF) peptide interactions with copper. Linear regression models based on the valence connectivity index of the 3^rd order (³χ^v) reproduced experimental stability constants (log β) for 1N, 2N, 3N, and 4N coordinated complexes with the standard error of 0.30-0.39 log β units. We developed separate models for seven tyrosinic (N=28) and five non-tyrosinic peptides (N=20), and a common model for both kinds of peptides (N=48) with an indicator (dummy) variable. The results indicate additional aromatic stabilisation in 4N complexes due to metal cation-π interactions with tyrosine but not with the phenylalanine residue. We have also amended the log K and log K^* values to correct miscalculations  published by Janicka-Klos et al. in 2013.