title: Cleavage agents for soluble oligomers of human islet amyloid polypeptide.
abstract: Soluble oligomers of human islet amyloid polypeptide (h-IAPP) are implicated in the initiation of beta-cell apoptosis leading to type 2 diabetes mellitus (T2DM). Cleavage of the h-IAPP included in an oligomer may provide a novel method for reducing the level of h-IAPP oligomers, offering a new therapeutic option for T2DM. From the combinatorial library of triazine derivatives prepared by exploiting the Co(III) complex of cyclen as the cleavage center for peptide bonds, eight compounds were selected as cleavage agents for oligomers of h-IAPP. After reaction with cleavage agents for 36 h at 37 degrees C and pH 7.50, up to 20 mol% of h-IAPP (initial concentration: 4.0 microM) was cleaved, although the target oligomers existed as transient species. Considerable activity was manifested at agent concentrations as low as 100 nM.
authors.affiliation: Department of Chemistry, Seoul National University, Seoul, 151-747, South Korea. jhsuh@snu.ac.kr
authors.forename: Junghun
authors.initials: J
authors.lastname: Suh
authors.forename: Woo Suk
authors.initials: WS
authors.lastname: Chei
authors.forename: Tae Yeon
authors.initials: TY
authors.lastname: Lee
authors.forename: Min Gyum
authors.initials: MG
authors.lastname: Kim
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Yoo
authors.forename: Keunhong
authors.initials: K
authors.lastname: Jeong
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Ahn
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D005374:Filtration; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007202:Indicators and Reagents; D058228:Islet Amyloid Polypeptide; D007536:Isomerism; D010446:Peptide Fragments / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014227:Triazines / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D007202:Indicators and Reagents; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D014227:Triazines; C075222:amyloid beta-protein (1-42)