Design and synthesis of novel fluoropeptidomimetics as potential mimics of the transition state during peptide hydrolysis.
alpha-Fluoroamino acids were targeted in our ongoing efforts to design novel fluoropeptidomimetics (1) as potential protease inhibitors. alpha-Fluoroglycine derivative (2) and alpha-fluoro-beta-aminoethanethiol derivatives (3-9) were synthesized for the first time en route to obtain the peptidomimetic moiety 1. The stability of 2-9 was investigated under organic as well as aqueous conditions. The stability of 3-9 under acidic and basic conditions, the effect of substitution at C-2 position, and potential biological activities are discussed.
Annedi
Subhash C
SC
Faculty of Pharmacy, Molecular Design and Information Technology Center, Department of Chemistry, University of Toronto, 19 Russell Street, Toronto, Ontario, M5S 2S2, Canada.
Li
Weiyong
W
Samson
Sheeba
S
Kotra
Lakshmi P
LP
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D006845:Hydrocarbons, Fluorinated; D010455:Peptides; D011480:Protease Inhibitors