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Cu II Coordination Chemistry of Patellamide Derivatives: Possible Biological Functions of Cyclic Pseudopeptides
Author(s) -
Comba Peter,
Dovalil Nina,
Gahan Lawrence R.,
Haberhauer Gebhard,
Hanson Graeme R.,
Noble Christopher J.,
Seibold Björn,
Vadivelu Prabha
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201101975
Subject(s) - chemistry , electron paramagnetic resonance , reactivity (psychology) , coordination complex , cyclic peptide , crystallography , density functional theory , peptide , titration , computational chemistry , stereochemistry , organic chemistry , metal , nuclear magnetic resonance , medicine , biochemistry , physics , alternative medicine , pathology
Two synthetic derivatives of the naturally occurring cyclic pseudooctapeptides patellamide A–F and ascidiacyclamide, that is, H 4 pat 2 , H 4 pat 3 , as well as their Cu II complexes are described. These cyclic peptide derivatives differ from the naturally occurring macrocycles by the variation of the incorporated heterocyclic donor groups and the configuration of the amino acids connecting the heterocycles. The exchange of the oxazoline and thiazole groups by dimethylimidazoles or methyloxazoles leads to more rigid macrocycles, and the changes in the configuration of the side chains leads to significant differences in the folding of the cyclic peptides. These variations allow a detailed study of the various possible structural changes on the chemistry of the Cu II complexes formed. The coordination of Cu II with these macrocyclic species was monitored by high‐resolution electrospray mass spectrometry (ESI‐MS), spectrophotometric (UV/Vis) and circular dichroic (CD) titrations, and electron paramagnetic resonance (EPR) spectroscopy. Density functional theory (DFT) calculations and molecular mechanics (MM) simulations have been used to model the structures of the Cu II complexes and provide a detailed understanding of their geometric preferences and conformational flexibility. This is related to the Cu II coordination chemistry and the reactivity of the dinuclear Cu II complexes towards CO 2 fixation. The variation observed between the natural and various synthetic peptide systems enables conclusions about structure–reactivity correlations, and our results also provide information on why nature might have chosen oxazolines and thiazoles as incorporated heterocycles.