Unnatural amino acids, the non-proteinogenic amino acids that either occur naturally or are chemically synthesized, are important tools for modern drug discovery research. Due to their unlimited structural diversity and functional versatility, they are widely used as chiral building blocks and molecular scaffolds in constructing combinatorial libraries.1 They represent a powerful tool in drug discovery when incorporated into therapeutic peptidomimetics and peptide analogs. Used as molecular probes they can help to better understand the function of biological systems.2
Peptidomimetics have found widespread recognition as surrogates for therapeutic peptides derived from proteinacious amino acids because they may show improved in vivo stability, enhanced potency, better oral absorption, improved tissue distribution, and increased selectivity of biological response. In this context, unnatural amino acids can be used to alter the tertiary structure of a peptide. Side chain modifications allow the design of drug candidates with a perfect match to their biological target.
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