NOVEL ALPHA-GLUCOSIDASE INHIBITORS IDENTIFIED USING MULTIPLE CYCLIC PEPTIDE COMBINATORIAL LIBRARIES

Twenty-six cyclic synthetic peptide combinatorial libraries (disulfide s and lactams) of varying size and composition, representing 6.8 x 10( 3) to 4.7 x 10(7) individual peptides, were synthesized along with the ir respective linear analogs. One of the hexapeptide lactam libraries (cyclo[xXxXxN]) was found to have significant alpha-glucosidase inhibi tory activity. This library was carried through an iterative process o f synthesis and screening, during which all of the five mixture positi ons (x and X) were successively defined. As the result of this process , potent and selective alpha-glucosidase inhibitors were identified.