Journal of Inclusion Phenomena and Molecular Recognition in Chemistry 26:185-195, 1996. 18 5 @ 1996 Kluwer Academic Publishers. Printed in the Netherlands. The Binding of Free Oligopeptides to Cyclodextrins: The Role of the Tyrosine Group EVAN J. BEKOS, JOSEPH A. GARDELLA, JR. and FRANK V. BRIGHT* Department of Chemistry, Natural Sciences and Mathematics Complex, State University of New York at Buffalo, Buffalo, NY 14260-3000, U.S.A. (Received: 15 November 1995; in final form: 22 July 1996) Abstract. The formation of c~-cyclodextrin (c~-CD) and fl-cyclodextrin (/3-CD) inclusion complexes with free tyrosine and the tyrosine residues within two free oligopeptides were investigated using steady-state fluorescence spectroscopy. The oligopeptides consist of five amino acids (pentapeptide) and the tyrosine residues are located at the n-termini. The two peptides used in this study have well- known biological functions and are known to bind selectively to specific cell receptors. Cyclodextrins were used to model this receptor-peptide (protein-ligand) interaction. Equilibrium binding constants and the enthalpy and entropy of binding were recovered. Molecular size of the tyrosine-containing species and pH (7.0 vs. 10.0) were found to have little affect on c~-CD binding. However, tyrosine binding to fl-CD was dependent on the size (free tyrosine vs. peptide), structure, and pentapeptide conformation. Key words: Fluorescence, minimal peptides, tyrosine residues, cooperativity, cyclodextrins. 1. Introduction Previous work from our laboratories has focused on producing specific cellular responses from minimal peptide sequences (MPS) covalently bound to fluoropoly- mer surfaces [1-3]. Minimal peptide sequences are the smallest sequential set of amino acids, from a larger protein unit, necessary to elicit a specific response. These MPS are known to promote specific cellular responses on binding to cell-surface receptors (integrins) [4, 5]. Adhesive proteins (e.g., fibronectin, vitronectin, fib- rinogen) and extracelluar matrices (e.g., laminin, collagen, von Willebrand factor) have several binding sites for integrin-cell surface receptors [6]. Integrin receptor proteins are known to connect the cell interior to its exterior environment and allow the cell to 'see' and 'feel' its environment and respond accordingly. Integrin receptors can also recognize cell binding domains of three to five sequential amino acids within larger proteins. An MPS of particular interest to us is a peptide fragment of laminin, tyr-ile- gly-ser-arg (YIGSR). YIGSR interacts specifically with the integrin receptors on certain neuronal cells [ 1,3, 7]. The enkephalin YGGFL (tyr-gly-gly-phe-leu) serves as the body's naturally-formed opiate and they bind to brain receptor sites, where * Author for correspondence.