Peptides in molecular recognition: synthetic and conformational aspects.

Abstract

Introduction Proteins play a crucial role in many molecular recognition processes. Over the past few years, thanks to the effort of several research laboratories, we have learned something of the mechanisms that regulate these interactions [ 11. Peptide molecules have served, and are serving, as model compounds in these kinds of studies. Nevertheless, slowly, as we learn more about the basis of molecular recognition, we are starting to have a certain predictive ability. A reliable predictive capability would open the door to the design and synthesis of peptide molecules which have as an inherent characteristic a certain molecular-recognition feature. As illustrated in Figure 1, from a purely 'host-guest chemistry' point of view, peptide molecules provide a series of advantageous features that can be exploited for the design of new compounds. Hydrogen bonding has been recognized as one of the most efficient non-covalent interactions and we can use the tendency of the peptide backbone to form intraand inter-chain hydrogen bonds to mould the global shape of the molecule. Chirality at the a-carbon provides the opportunity of exploring several 'configurational versions' of the molecule; because we are using chemical synthesis, we are not constrained to use only the homochiral 1.-amino acid series. We can exploit the wealth of functional groups available at the amino acid side chains to improve, or modulate, the recognition properties of our compounds. We can use our present knowledge of peptide and protein conformational analysis to control, to some extent, the three-dimensional structure of our compounds. Finally, but also very importantly, we have at our disposal efficient synthetic methods for the preparation of peptides. In addition to the already enumerated possible control elements, we have another possibility for the design of new peptides for molecular-recognition studies: formation of disulphide bridges between cysteine residues. In this paper we will focus on this aspect.