Interactions of oligomers of organic polyethers with histidine amino acid

RATIONALE Knowledge on noncovalent intermolecular interactions of organic polyethers with amino acids is essential to gain a better understanding on how polymers assemble in organic nanoparticles which are promising for drug delivery and cryoprotection. The main objective of the present study was to determine how polyethers assemble around ionizable amino acids such as histidine. METHODS Electrospray mass spectrometry was applied to probe the interactions in model systems consisting of polyethylene glycol PEG‐400 or oxyethylated glycerol OEG‐5 and amino acid histidine hydrochloride. Molecular dynamics simulation was utilized to visualize the structure of complexes of polyether oligomers with histidine in different charge states. RESULTS Stable gas‐phase clusters composed of polyether oligomers (PEGn, OEGn) with protonated histidine ‐ PEGn•His•H+, OEGn•His•H+, OEGn•OEGm•His•H+ and chlorine counterion – PEGn•Cl‐, OEGn•Cl‐, were observed under electrospray conditions. Molecular dynamics simulation of representative polyether‐histidine complexes revealed the stabilization of oligomers by multiple hydrogen and coordination bonds whereby charged groups are wrapped by the polymeric chains. CONCLUSIONS The self‐organization of polyether chains around the protonated imidazole group of histidine was revealed. This finding should be considered when modelling a pegylated protein structure and polyether‐based organic nanoparticles. Copyright © 2012 John Wiley & Sons, Ltd.