Enhancing peptide antigenicity by helix stabilization

Gurunath, Ramanathan and Beena, TK and Adiga, PR and Balaram, P (1995) Enhancing peptide antigenicity by helix stabilization. In: FEBS Letters, 361 (2-3). pp. 176-178.

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Abstract

The engineering of antigenic determinants on super secondary structures using de novo design approaches often involves synthesis of long peptide chains (35--80 residues long). This communication illustrates that the stabilization of secondary structure by rational design can also greatly enhance immunogenicity and antigenicity, but in much shorter peptide sequences (21 residues long). A peptide epitope the sequence of which has been derived from the C-terminus of the chicken riboflavin carrier protein (cRCP), H2N-Tyr-His-Ala-Cys-Gln-Lys-Lys-Leu-Leu-Lys-Phe-GIu-AIa-Lm-GIn-GIn-GIu-Giu-GIy-GIu-GIu-OH, has been chosen for analysis. Helical conformations were induced in the peptide in aqueous trifluoroetbanol. Analogs were designed to stabilize this conformation in water by either the introduction of appropriately spaced ion pairs or the strongly helix nucleating residue a-aminoisobutyric acid (Aib), substituted for Ala/Gly, thus affording a comparison of the helix stabilization strategies. Circular dichroism (CD) results demonstrate that all the designed analogs are appreciably more helical than the parent peptide in 50% aqueous trifluoroethanol. Peptide antisera were raised for all analogs in rabbits. The affinities of these antisera for the native protein antigen, determined using a chaotrope disrupted binding assay, correlated very well with the helix content determined by CD.

Item Type:	Journal Article
Publication:	FEBS Letters
Publisher:	Elsevier Science
Additional Information:	Copyright for this article belongs to Elsevier Science.
Keywords:	Peptide antigenicity;Helix stabilization;De novo design; Riboflavin carrier protein;Circular dichroism;Peptide conformation
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Biological Sciences > Biochemistry
Date Deposited:	08 Nov 2004
Last Modified:	01 Mar 2012 05:53
URI:	http://eprints.iisc.ac.in/id/eprint/2277

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