Photochemical and Structural Studies on Cyclic Peptide Models.

Ultra-violet (UV) irradiation has a significant impact on the structure and function of proteins that is supposed to be in relationship with the tryptophan-mediated photolysis of disulfide bonds. To investigate the correlation between the photoexcitation of Trp residues in polypeptides and the associated reduction of disulfide bridges, a series of small, cyclic oligopeptide models were analyzed in this work. Average distances between the aromatic side chains and the disulfide bridge were determined following molecular mechanics (MM) geometry optimizations.

Development of cyclic NGR peptides with thioether linkage: structure and dynamics determining deamidation and bioactivity.

NGR peptides that recognize CD13 receptors in tumor neovasculature are of high interest, in particular due to their potential applications in drug targeting. Here we report the synthesis and structural analysis of novel thioether bond-linked cyclic NGR peptides. Our results show that their chemostability (resistance against spontaneous decomposition forming isoAsp and Asp derivatives) strongly depends on both sample handling conditions and structural properties.

Comprehensive chiroptical study of proline-containing diamide compounds.

The continuously growing interest in the understanding of peptide folding led to the conformational investigation of methylamides of N-acetyl-amino acids as diamide models. Here we report the results of detailed conformational analysis on Ac-Pro-NHMe and Ac-β-HPro-NHMe diamides. These compounds were analyzed by experimental and computational methods, the conformational distributions obtained by Density Functional Theory (DFT) calculations for isolated and solvated diamide compounds are discussed.

Is β-homo-proline a pseudo-γ-turn forming element of β-peptides? An IR and VCD spectroscopic study on Ac-β-HPro-NHMe in cryogenic matrices and solutions.

In order to test the pseudo-γ-turn forming capability of β-homo-proline (β(3)-HPro) 2-[(2S)-1-acetylpyrrolidin-2-yl]-N-methylacetamide (Ac-β(3)-HPro-NHMe) was synthesized and its potential energy landscape was investigated by infrared (IR) and vibrational circular dichroism (VCD) spectroscopy combined with density functional calculations. Based upon a comparison between experimental and computed spectra three different pseudo-γ-turn-like trans conformers and a cis conformer were identified in low-temperature Ar and Kr matrices. The computations in agreement with the observations reveal that, in contrast to its α-Pro analogue, the room-temperature abundance of the cis conformer is significant, falling above 10% in the isolated phase.