Design of Peptides and Proteins

Abstract

This chapter focuses on contemporary approaches to the design of structurally defined peptides and proteins with special emphasis being given to the ways in which this approach has elucidated the structural basis for the function of a variety of natural molecules. When in their proper biological milieu, peptides and proteins assume fairly well-defined conformations, which are responsible for their biological and physical properties. The mechanisms by which these molecules adopt defined three-dimensional structures depend on their size and chemical compositions. There are a variety of strategies and approaches for protein and peptide design. Those adopted for a given problem will depend on the size and molecular characteristics of the desired target molecule. If one wishes to create a model for a small peptide (e.g., the pentapeptide hormone enkephalin), then it might be feasible to design an analog of this molecule that is locked into a biologically active conformation. The design of proteins that adopt predetermined three-dimensional structures is perhaps the most ambitious goal, and one that has been attacked only recently. The design of conformationally constrained peptides is a powerful method for elucidating the biologically active conformation of a peptide when it is bound to its receptor. The design of medium-sized peptides is beset with many of the same problems encountered in the design of small peptides. Medium-sized peptides are also very flexible and tend to lack defined conformations at room temperature in aqueous solutions.