Peptidomimetic building blocks for drug discovery:

We have developed new asymmetric and enantioselective routes for the preparation of a variety of conformationally constrained peptidomimetic building blocks. These molecules include a-methylcysteine, a-methylthreonine, do-threonine, a$-dimethylcysteine, a,P-dimethyltryptophan, twisted amide, and substituted lanthionine structures. It has been shown that these molecules are very useful building blocks for the peptidomimetic drug design. In the past two decades, a wide variety of naturally occurring peptides have been discovered. These peptides play very important biological roles as hormones, enzyme inhibitors, substrates, neurotransmitters and immunomodulators among others. After binding to their corresponding receptors or enzymes, they can influence cell-cell communication and control a series of vital functions such as metabolism, immune defense, digestion, respiration, sensitivity to pain, reproduction, behavior, and electrolyte levels. Thus, extensive studies have been undertaken in an effort to understand the physiological effects of these peptidic molecules toward the design of new peptide-based therapeutic agents. For peptide-based drug design, there are several major considerations that limit clinical applications such as: (1) rapid degradation by many specific or nonspecific peptidases under physiological conditions