Modelling of copper(II) binding to pentapeptides related to atrial natriuretic factor using the 3χv connectivity index / Modeliranje vezivanja bakra(II) za pentapeptide povezane s atrijalnim natriuretičkim faktorom pomoću indeksa povezanosti 3χv

Ante Miličević,Nenad Raos

doi:10.1515/aiht-2015-66-2631

Abstract

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 3rd order (3χv) 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

Highlights

Using model molecular graph system for atrial theory we natriuretic sftaucdtoierd(AthNeFb)inpdeipntgidoefiNntSerFaRcYtio-NnsHw2 iatnhdc1o2ppreerl.aLteidnepaernrteagpreepstsidioenammoiddeeslstobaCseud(IoI)natshae valence connectivity index of the 3rd order (3χv) reproduced experimental stability constants for 1N, 2N, 3N, and KEY WORDS: coordination compounds; peptides; stability constants; topological indices
Atrial natriuretic factor (ANF) is a peptide hormone secreted by the heart to control extracellular fluid volume and blood pressure by maintaining water and salt balance [1, 2]
All ANF peptides have the same C-terminal sequence, NSFRY, and the same 17-residue disulphide-bonded core, which is essential for their function [1]

Summary

Introduction

Using model molecular graph system for atrial theory we natriuretic sftaucdtoierd(AthNeFb)inpdeipntgidoefiNntSerFaRcYtio-NnsHw2 iatnhdc1o2ppreerl.aLteidnepaernrteagpreepstsidioenammoiddeeslstobaCseud(IoI)natshae valence connectivity index of the 3rd order (3χv) reproduced experimental stability constants (log β) for 1N, 2N, 3N, and KEY WORDS: coordination compounds; peptides; stability constants; topological indices. All ANF peptides have the same C-terminal sequence, NSFRY, and the same 17-residue disulphide-bonded core, which is essential for their function [1]. Using a variety of methods, Janicka-Klos et al [5] systematically analysed Cu(II) binding to pentapeptides mimicking the N-terminal sequence of ANF [5]. Beside NSFRY-NH2, the peptide with the same sequence as the terminal part of ANF, they investigated its analogues in order to see how residues of the model peptide affected Cu(II) binding. These models proved suitable for peptides, giving the standard error of prediction of 0.2-0.3 log K units [26, 27]

Objectives

Methods

Results