Cu(II) cyclen cleavage agent for human islet amyloid peptide.
Type 2 diabetes mellitus (T2DM) is characterized by a substantial reduction in beta-cell mass and the amyloid fibrils which are formed by the aggregation of the human islet amyloid polypeptide (h-IAPP) in the islet of Langerhans. Cleavage agents with Co(III) cyclen as the catalytic group have been studied as a novel therapeutic option for T2DM patients. However, recent research has suggested that the cytotoxicity of h-IAPP might be mediated by interactions with Cu(II); furthermore, it has been shown in vitro that Cu(II) prevents h-IAPP from forming the beta-sheet conformers. Therefore, we synthesized a cleavage agent using Cu(II) cyclen. The resulting cleaved fragments and estimated cleavage yield (8.3mol%) were evaluated after incubation with h-IAPP.
Department of Chemistry, Korea Military Academy, Seoul 139-799, Republic of Korea. doas1mind@kma.ac.kr
Keunhong
K
Jeong
Woo Young
WY
Chung
Young-Sik
YS
Kye
Dongwook
D
Kim
D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D002384:Catalysis; D003300:Copper; D016213:Cyclins / Q000138:chemical synthesis* / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D006801:Humans; D007515:Islets of Langerhans / Q000737:chemistry*; D008968:Molecular Conformation; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D016564:Amyloid beta-Protein Precursor; D016213:Cyclins; D010446:Peptide Fragments; D003300:Copper