Novel alpha-glucosidase inhibitors identified using multiple cyclic peptide combinatorial libraries.
Twenty-six cyclic synthetic peptide combinatorial libraries (disulfides 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 their respective linear analogs. One of the hexapeptide lactam libraries (cyclo[xXxXxN]) was found to have significant alpha-glucosidase inhibitory activity. This library was carried through an iterative process of synthesis and screening, during which all of the five mixture positions (x and X) were successively defined. As the result of this process, potent and selective alpha-glucosidase inhibitors were identified.
Eichler
J
J
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
Lucka
A W
AW
Pinilla
C
C
Houghten
R A
RA
D000595:Amino Acid Sequence; D019020:Directed Molecular Evolution / Q000379:methods*; D004220:Disulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D065089:Glycoside Hydrolase Inhibitors; D066298:In Vitro Techniques; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D004220:Disulfides; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007769:Lactams; D019151:Peptide Library; D010456:Peptides, Cyclic