β-lactam antibiotics epitope mapping with STD NMR spectroscopy: a study of drug-human serum albumin interaction

Cíntia D F Milagre,Wanda P Almeida,Luís F Cabeça,Anita J Marsaioli

doi:10.1590/s0103-50532012000300005

Abstract

Molecular recognition events are key issues in many biological processes. STD NMR (saturation transfer difference nuclear magnetic resonance spectroscopy) is one of the techniques used to understand such biological interactions. Herein, we have investigated the interactions of four β-lactam antibiotics belonging to two classes (cephalosporins and penicillins) with human serum albumin (HSA) by 1H STD NMR revealing that the interaction between the aromatic moiety and HSA is responsible for the binding efficiency. Thus, the structural differences from the five to six-membered thio ring in penicillins and cephalosporins do not seem to influence antibiotic-albumin interactions.

Highlights

Understanding the molecular processes that govern the behavior and pharmacokinetics of drug-drug and drug-plasma protein in vivo is of upmost interest with an increasing appreciation of the role of human serum albumin (HSA) on the effective activity of drugs at their site of action.[1]
The STD spectrum provided epitope mapping with values obtained from the individual signal intensities in the STD spectrum on resonance (Ion) and in the reference nuclear magnetic resonance (NMR) spectrum off resonance (Ioff)
The epitope maps of 1, 2, 3 and 4 to HSA determined in this study indicate that in all four antibiotics, the aromatic moiety plays an important role in drug-protein anchorage and showed that the change from five to sixmembered thio ring does not seem to influence those antibiotic-HSA interactions

Summary

Introduction

Understanding the molecular processes that govern the behavior and pharmacokinetics of drug-drug and drug-plasma protein in vivo is of upmost interest with an increasing appreciation of the role of human serum albumin (HSA) on the effective activity of drugs at their site of action.[1]. All STD experiments were selectively saturated using the Gaussian train pulses at −0.5 ppm for the on-resonance (Ion) and at 30 ppm for (Ioff) in which no protein signal was detected and for the STD control.

Results

Conclusion