Conformations of Heterochiral and Homochiral Proline-Pseudoproline Segments in Peptides: Context Dependent Cis-Trans Peptide Bond Isomerization

Kantharaju, Kantharaju and Raghothama, Srinivasarao and Raghavender, Upadhyayula Surya and Aravinda, Subrayashastry and Shamala, Narayanaswamy and Balaram, Padmanabhan (2009) Conformations of Heterochiral and Homochiral Proline-Pseudoproline Segments in Peptides: Context Dependent Cis-Trans Peptide Bond Isomerization. In: Biopolymers, 92 (5). pp. 405-416.

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Abstract

The pseudoproline residue (Psi Pro, L-2,2-dimethyl-1,3-thiazolidine-4-carboxylic acid) has been introduced into heterochiral diproline segments that have been previously shown to facilitate the formation of beta-hairpins, containing central two and three residue turns. NMR studies of the octapeptide Boc-Leu-Phe-Val-(D)Pro-Psi Pro-Leu-Phe-Val-OMe (1), Boc-Leu-Val-Val-(D)Pro-Psi Pro-Leu-Val-Val-OMe (2), and the nonapeptide sequence Boc-Leu-Phe-Val-(D)Pro-Psi Pro-(D)Ala-Leu-Phe-Val-OMe (3) established well-registered beta-hairpin structures in chloroform solution, with the almost exclusive population of the trans conformation for the peptide bond preceding the Psi Pro residue. The beta-hairpin conformation of 1 is confirmed by single crystal X-ray diffraction. Truncation of the strand length in Boc-Val-(D)Pro-Psi Pro-Leu-OMe (4) results in air increase in the population of the cis conformer, with a cis/trans ratio of 3.65. Replacement of Psi Pro in 4 by (L)Pro in 5, results in almost exclusive population of the trans form, resulting in an incipient beta-hairpin conformation, stabilized by two intramolecular hydrogen bonds. Further truncation of the sequence gives an appreciable rise in the population of cis conformers in the tripeptide piv-(D)Pro-Psi Pro-Leu-OMe (6). In the homochiral segment Piv-Pro Psi Pro-Leu-OMe (7) only the cis form is observed with the NMR evidence strongly supporting a type VIa beta-turn conformation, stabilized by a 4 -> 1 hydrogen bond between the Piv (CO) and Leu (3) NH groups. The crystal structure of the analog peptide 7a (Piv-Pro-Psi(H,CH3)Pro-Leu-NHMe) confirms the cis peptide bond geometry for the Pro-Psi(H,CH3)pro peptide bond, resulting in a type VIa beta-turn conformation.

Item Type:	Journal Article
Publication:	Biopolymers
Publisher:	John Wiley & Sons, Inc.
Additional Information:	Copyright of this article belongs to John Wiley & Sons, Inc., 2009
Keywords:	pseudoproline; peptides; cis-trans isomerization; NMR; turn
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility) Division of Physical & Mathematical Sciences > Physics
Date Deposited:	27 Oct 2009 12:07
Last Modified:	19 Sep 2010 05:50
URI:	http://eprints.iisc.ac.in/id/eprint/24553

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