Chem. Pharm. Bull. 55(3) 349—358 (2007)

The design and synthesis of new molecules having various functions, which can not be attained by using natural products, have attracted much attention from organic, bioorganic, peptide, and medicinal chemists. The creation of such intelligently functionalized molecules is a new research area of chemistry in the 21st century. One category of such molecules might be ‘foldamers’, as named by Gellman. The foldamers are any polymer with a strong tendency to adopt a specific compact conformation. Natural enzymes and receptors, which form defined three-dimensional shapes and have biological functions, might be the ultimate ‘foldamers’ designed and produced by evolution in nature. Unfortunately, oligopeptides composed of natural L-a-amino acids often form unordered or unstable secondary structures, particularly in the case of short peptides because of the flexibility of natural amino acids. The unordered or unstable secondary structure of natural oligopeptides is a drawback in the use of the oligopeptides as drug candidates, biological probes, and functionalized-device molecules. Thus, organic chemists are devoting great efforts to the design of new amino acid analogs and their oligomers with conformational restrictions.