Pregabalin peptides: conformational comparison of gamma(3)- and gamma(4)-substituted gamma-amino acids in alpha gamma alpha alpha alpha pentapeptides

Basuroy, Krishnayan and Kantharaju, Kamanna and Aravinda, Subrayashastry and Shamala, Narayanaswamy and Balaram, Padmanabhan (2019) Pregabalin peptides: conformational comparison of gamma(3)- and gamma(4)-substituted gamma-amino acids in alpha gamma alpha alpha alpha pentapeptides. In: AMINO ACIDS, 51 (9). pp. 1297-1306.

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Abstract

Gamma-aminobutyric acid (GABA, gammaAbu), an unsubstituted gamma-amino acid, is an important inhibitory neurotransmitter in the mammalian brain. The role of GABA in the treatment of epilepsy has triggered a great deal of interest in substituted gamma-amino acids, which may serve as GABA analogs, acting as inhibitors of GABA aminotransferase. Pregabalin (Pgn), a well-known antiepileptic drug, is also a beta-substituted gamma3-amino acid. Pregabalin and gamma4Leu, an isomer of the pregabalin (Pgn) residue, both carrying the same isobutyryl group in the side chain, were introduced in the present study to have a comparison of their respective conformational differences as well as their role in influencing the overall conformation of the peptides, they are inserted in. Two alpha-gamma-alpha-alpha-alpha hybrid pentapeptides were designed that contain Aib-Pgn and Aib-gamma4Leu segments at the N terminus. The study provides a detailed analysis of the conformational properties and non-covalent interactions observed in the crystal structures of two polymorphs of the pentapeptide monohydrate, Boc-Aib-(S)Pgn-Leu-Phe-Val-OMe (C38H63N5O8 center dot H2O) and the isomeric pentapeptide, Boc-Aib-gamma4(R)Leu-Leu-Phe-Val-OMe (C38H63N5O8), obtained from single crystal X-ray diffraction experiments.

Item Type:	Journal Article
Publication:	AMINO ACIDS
Publisher:	SPRINGER WIEN
Additional Information:	copyright for this article belongs to SPRINGER WIEN
Keywords:	gamma-residues; Hybrid-peptides; Conformational analysis; X-ray diffraction
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Physical & Mathematical Sciences > Physics
Date Deposited:	21 Oct 2019 11:21
Last Modified:	21 Oct 2019 11:21
URI:	http://eprints.iisc.ac.in/id/eprint/63734

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