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Volume 375, Issue 1-2 p. 15-17
Research letter
Free Access

A novel approach to the design of potent bioactive peptides by incorporation of proline brackets: antiplatelet effects of Arg-Gly-Asp peptides

R. Manjunatha Kini

R. Manjunatha Kini

Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0614, USA

Present address: Bioscience Centre, Faculty of Science, National University of Singapore, Lower Kent Ridge Road, Singapore 0511, Republic of Singapore. Fax: (65) 779-2486. Search for more papers by this author
Herbert J. Evans

Herbert J. Evans

Department of Biochemistry and Molecular Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0614, USA

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First published: November 13, 1995
Citations: 30
Corresponding author.

Abstract

Enhancing the potency of peptides is a critical and important step in the development of peptide drugs. We have proposed that proline residues flanking protein-protein interaction sites perform a structural role in enhancing their interaction [R.M. Kini and H.J. Evans, Biochem. Biophys. Res. Commun. 212 (1995) 1115–1124]. To test this theory, we incorporated proline residues on either or both sides of the interaction site of an antiplatelet peptide, IARGDMNA and determined the inhibitory potency of the peptides in whole blood aggregation. Inclusion of one proline residue, on either the amino or carboxy terminal side of the interaction site, enhances the antiplatelet activity to approximately the same extent (1.5- to 2.5-fold). Incorporation of proline residues on both sides enhances the activity by 7- to 13-fold. This enhancement of the biological activity of the peptide is probably due to a reduction in the number of possible conformations of the peptide, without introducing the rigidity that would accompany cyclization. Incorporation of proline brackets thus provides a novel approach to the design and development of more potent peptide drugs and ligands.