title: Peptide-cleaving agents for human islet amyloid polypeptide containing substrate recognition site based on quinoxaline: cleavage efficiency enhanced by lowering substrate concentration.
abstract: Oligomers of human islet amyloid polypeptide (h-IAPP) are believed to be the pathogenic species for type 2 diabetes mellitus. Peptide-cleaving agents selective for oligomers of h-IAPP were synthesized by using quinoxaline derivatives as recognition sites attached to the Co(III) complex of cyclen in this study. When the initial concentration of h-IAPP was lowered from 4.0 to 0.20 μM, cleavage yield of the new agents was enhanced by 3 times reaching 16-22 mol%. This shows that the agents would have significant activities at subnano molar concentrations if the concentration of h-IAPP is lowered to the in vivo values. This further indicates that the peptide-cleaving agents prepared previously in this laboratory possess sufficiently high activity for application as a new therapeutic option for Alzheimer's disease, type 2 diabetes mellitus, and Parkinson's disease.
authors.affiliation: Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Woosuk
authors.initials: W
authors.lastname: Chei
authors.forename: Heeyeon
authors.initials: H
authors.lastname: Ju
authors.forename: Junghun
authors.initials: J
authors.lastname: Suh
mesh_terms: D003035:Cobalt / Q000737:chemistry; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000187:drug effects*; D008954:Models, Biological; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
chemical_list: D058228:Islet Amyloid Polypeptide; D009942:Organometallic Compounds; D011810:Quinoxalines; D003035:Cobalt