SCHEME 1.

Summary of methods employed for biological production of backbone-cyclized peptides. Left panel, these approaches rely on the ribosomal synthesis of a polypeptide precursor that undergoes cyclization mediated by inteins or proteases. Middle panel, shown are three-dimensional structures of three examples of naturally occurring circular peptides with potential biotechnological value. MCoTI-II and SFTI-1 are powerful protease inhibitors and are attractive scaffolds for the introduction of other biological activities. RTD-1 is a θ-defensin that has strong antimicrobial and anti-inflammatory properties. All have been successfully expressed in biological systems (see Table 1). Right panel, the potential biotechnological applications of circular polypeptides, which include pharmacological, agrochemical, and diagnostic applications, are summarized. Molecular structures were generated using the structures of MCoTI-II (Protein Data Bank code 1IB9), SFTI-1 (code 1JBN), and RTD-1 (code 1HVZ).