Structure analysis of proteins, peptides and metal complexes by vibrational circular dichroism

There are two principal forms of vibrational optical activity (VOA), an IR form referred to as vibrational circular dichroism (VCD) and Raman form known as Raman optical activity (ROA). This paper reports examples of the application of VCD spectroscopy for the determination of the absolute configuration and conformation of chiral molecules, e. g. cyclic beta-lactams. VCD spectroscopy can be applied for the characterization of the conformation of proteins and peptides in solution. VCD based conformational analysis of cyclic peptides is discussed. Examples are the cyclic hexapeptide cyclo(Pro(2)-Gly-Pro(2)-Gly) and cyclic peptides comprising beta-homoamino acids (trans-2-aminocyclopentane or trans-2-aminocyclohexane carboxylic acid). Structure analysis by VCD of opiate peptides, glycopeptides, peptidomimetics and chiral transition metal complexes are also discussed

VCD studies on cyclic peptides assembled from L-alpha-amino acids and a trans-2-aminocyclopentane- or trans-2-aminocyclohexane carboxylic acid

Vass E, Strijowski U, Wollschlaeger K, et al. VCD studies on cyclic peptides assembled from L-alpha-amino acids and a trans-2-aminocyclopentane- or trans-2-aminocyclohexane carboxylic acid. Journal of Peptide Science. 2010;16(11):613-620.The increasing interest in peptidomimetics of biological relevance prompted us to synthesize a series of cyclic peptides comprising trans-2-aminocyclohexane carboxylic acid (Achc) or trans-2-aminocyclopentane carboxylic acid (Acpc). NMR experiments in combination with MD calculations were performed to investigate the three-dimensional structure of the cyclic peptides. These data were compared to the conformational information obtained by electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectroscopy. Experimental VCD spectra were compared to theoretical VCD spectra computed quantum chemically at B3LYP/6-31G(d) density functional theory (DFT) level. The good agreement between the structural features derived from the VCD spectra and the NMR-based structures underlines the applicability of VCD in studying the conformation of small cyclic peptides. Copyright 2010 European Peptide Society and John Wiley & Sons, Ltd

Study of dinuclear Rh(II) complexes of phenylalanine derivatives as potential anticancer agents by using X-ray fluorescence and X-ray absorption

In vitro antitumor efficacy of several dinuclear bridgings and one chelate structure dirhodium(II) complex of N-protected phenylalanine derivatives were tested on HT-29 cells. The following synthesized and previously characterized complexes were applied in the present work: Rh-2(OAc)(4)(O-Phe-Z)(n) (n = 1-4, O--Phe-Z = N-benzyloxycarbonyl-L-phenylalaninate), Rh-2(OAc)(4-n)(O-Phe-Ac)(n) (n = 1-4, O--Phe-Ac = N-acetyl-L-phenylalaninate), Rh-2(OAc)(2)(N-Me-D-Phe-O)(2) corresponding to N-methyl-D-phenylalaninate as well as Rh-2(OAc)(4) (-OAc = acetate). Depending on the complex ligand type and its coordination number, the intracellular rhodium (Rh) content determined by total reflection X-ray fluorescence (TXRF) spectrometry in the HT-29 cells varied between 25 and 2500 ng/10(6) cells. In vitro cytotoxicity and cytostatic evaluations of the compounds on HT-29 human cell culture were performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay. Compared to Rh-2(OAc)(4), the Rh compounds containing one or two O--Phe-Z moieties proved to be the most effective on the HT-29 cells. Moreover, synchrotron radiation TXRF-X-ray absorption near edge structure measurements suggested a change of the molecular symmetry of the dirhodium(II) center for the moderately in vitro cytotoxic, lipophilic L-phenylalanine derivative complexes, characterized also by low ligand exchange rate when they were studied on HT-29 cells. (C) 2015 Elsevier B.V. All rights reserved