ABSTRACT
Peptidomimetic and nonpeptide drug discovery has evolved to become an extraordinarily intriguing area of interdisciplinary research. Peptides exhibit extraordinary molecular diversity by virtue of their varying primary structures. The three-dimensional structural properties of peptides are defined in terms of torsion angles between the backbone amine nitrogen, backbone carbonyl carbon, backbone me thine carbon, and side chain hydrocarbon functionalization derived from the amino acid sequence. A plethora of sophisticated synthetic chemistry approaches have entered into the arena of peptide-based molecular design, including well-established applications of unusual amino acids and dipeptide surrogates, among other types of chemical modifications. Historically, the major focus of peptidomimetic design has evolved from receptor-targeted drug discovery research and has not been directly impacted by an experimentally-determined 3D structure of the target protein. The convergence of structure-based drug design, synthetic chemical libraries, and high-throughput screening technologies have established a new paradigm for drug discovery.
