Cleavage agents for soluble oligomers of human islet amyloid polypeptide.
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.
Suh
Junghun
J
Department of Chemistry, Seoul National University, Seoul, 151-747, South Korea. jhsuh@snu.ac.kr
Chei
Woo Suk
WS
Lee
Tae Yeon
TY
Kim
Min Gyum
MG
Yoo
Sang Ho
SH
Jeong
Keunhong
K
Ahn
Jae Young
JY
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
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)