Tryptophan Residues: Scarce in Proteins but Strong Stabilizers of beta-Hairpin Peptides

Tryptophan plays important roles in protein stability and recognition despite its scarcity in proteins Except as fluorescent groups, they have been used rarely in peptide design Nevertheless, Trp residues were crucial for the stability-of some designed minimal proteins In 2000, Trp-Trp pairs were shown to contribute more than any othv hydrophobic interaction to the stability of beta-hairpin peptides Since then, Trp Trp pairs have emerged as a paradigm for the design of stable beta-hairpins, such as the Trpzip peptides Here, we analyze the nature of the stabilizing capacity of Trp Trp pairs by reviewing the beta-hairpin peptides containing Trp Trp pairs described up to now, the spectroscopic features and geometry of the Trp-Trp pairs, and their use as binding sites in beta-hairpin peptides To complete the overview, we briefly go through the other relevant beta-hairpin stabilizing Trp-non-Trp interactions and illustrate the use of Trp in the design of short peptides adopting a-helical and mixed alpha/beta motifs This review is of interest in the field of rational design of proteins, peptide, peptidomimetics, and biomaterials (C) 2010 Wiley Periodicals, Inc Biopolymers (Pept Sci) 94 779-790, 2010