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Design of a Peptide Hairpin Containing a Central Three-Residue Loop

Rai, Rajkishor and Raghothama, Srinivasarao and Balaram, Padmanabhan (2006) Design of a Peptide Hairpin Containing a Central Three-Residue Loop. In: Journal of American Chemical Society, 128 (8). 2675 -2681.

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Abstract

The construction of a designed $\beta$-hairpin structure, containing a central three-residue loop has been successfully achieved in the synthetic nonapeptide $Boc-Leu-Phe-Val-^DPro-^LPro-^DAla-Leu-Phe-Val-OMe$ (2). The design is based on expanding the two-residue loop established in the peptide $\beta$-hairpin $Boc-Leu-Phe-Val-^DPro-^LPro-Leu-Phe-Val-OMe$ (1). Characterization of the registered $\beta$-hairpins in peptides 1 and 2 is based on the observation of key nuclear Overhauser effects (NOEs) in $CDCl_3$ and $CD_3OH$. Solvent titration and temperature dependence of NH chemical shifts establish the identity of NH groups involved in interstrand hydrogen bonding. In peptide 2, the antiparallel registry is maintained, with the formation of a $^DPro-^LPro-^DAla$ loop, stabilized by a $5\rightarrow1$ hydrogen bond between Val3 CO and Leu7 NH groups $(C_{13}, \alpha-turn)$ and a $3\rightarrow1$ hydrogen bond between $^DPro4$ CO and $^DAla6$ NH groups $(C_7, \gamma-turn)$. NMR derived structures suggest that in peptide 2, $^DAla(6)$ adopts an $\alpha_L$ conformation. In peptide 1, the $^DPro-^LPro$ segment adopts a type II' $\beta$-turn. Replacement of $^DAla (6)$ in peptide 2 by $^LAla$ in peptide 3 yields a $\beta$-hairpin conformation, with a central $^DPro-^LPro$ two-residue loop. Strand slippage at the C-terminus results in altered registry of the antiparallel strands.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to American Chemical Society
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 02 Jun 2006
Last Modified: 19 Sep 2010 04:28
URI: http://eprints.iisc.ernet.in/id/eprint/7403

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