Conformational ensembles of flexible beta-turn mimetics in DMSO-d(6)
Loading...
Access rights
openAccess
acceptedVersion
URL
Journal Title
Journal ISSN
Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
This publication is imported from Aalto University research portal.
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
Date
Department
Major/Subject
Mcode
Degree programme
Language
en
Pages
Series
Organic and Biomolecular Chemistry, Volume 8, issue 9, pp. 2103-2116
Abstract
b-Turns play an important role in peptide and protein chemistry, biophysics, and bioinformatics. The aim of this research was to study short linear peptides that have a high propensity to form b-turn structures in solution. In particular, we examined conformational ensembles of b-turn forming peptides with a general sequence CBz-L-Ala-L-Xaa-Gly-L-Ala-OtBu. These tetrapeptides, APGA, A(4R)MePGA, and A(4S)MePGA, incorporate proline, (4R)-methylproline, and (4S)-methylproline, respectively, at the Xaa position. To determine the influence of the 4-methyl substituted prolines on the b-turn populations, the NAMFIS (NMR analysis of molecular flexibility in solution) deconvolution analysis for these three peptides were performed in DMSO-d6 solution. The NBO (natural bond orbital) method was employed to gain further insight into the results obtained from the NAMFIS analysis. The emphasis in the NBO analysis was to characterize remote intramolecular interactions that could influence the backbone-backbone interactions contributing to b-turn stability. NAMFIS results indicate that the enantiospecific incorporation of the methyl substituent at the Cg (C4) position of the proline residue can be used to selectively control the pyrrolidine ring puckering propensities and, consequently, the preferred f,y angles associated with the proline residue in b-turn forming peptides. The NAMFIS analyses show that the presence of (4S)-methylproline in A(4S)MePGA considerably increased the type II b-turn population with respect to APGA and A(4R)MePGA. The NBO calculations suggest that this observation can be rationalized based on an n→p* interaction between the N-terminus alanine carbonyl oxygen and the proline carbonyl group. Several other interactions between remote orbitals in these peptides provide a more detailed explanation for the observed population distributions.Description
Keywords
Other note
Citation
Koivisto, J J, Kumpulainen, E T T & Koskinen, A M P 2010, 'Conformational ensembles of flexible beta-turn mimetics in DMSO-d(6)', Organic and Biomolecular Chemistry, vol. 8, no. 9, pp. 2103-2116. https://doi.org/10.1039/b921794k