29 - Design of Peptidomimetics

Abstract

Peptidomimetics are powerful tools for the study of molecular recognition and provide a unique opportunity to dissect and investigate structure–function relationships in both peptides and complex proteins. There has been an increasing effort to rationally design and synthesize highly active analogs of biologically significant peptides and proteins. One approach to the design of peptidomimetics has been guided by the simple elegance that nature has employed in the molecular architecture of proteinaceous species. Three basic structural building blocks are utilized for the construction of all proteins. The design and synthesis of peptidomimetic prosthetic units to replace these three architectural motifs affords the opportunity to dissect and investigate complex structure–function relationships in proteins through the use of small synthetic conformationally restricted components. This is a critical step towards the rational design of low molecular weight nonpeptidic pharmaceutical agents, which are devoid of the shortcomings of conventional peptides.