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Cleavage agents for soluble oligomers of human islet amyloid polypeptide

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Abstract

Soluble oligomers of human islet amyloid polypeptide (h-IAPP) are implicated in the initiation of β-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 °C and pH 7.50, up to 20 mol% of h-IAPP (initial concentration: 4.0 μM) was cleaved, although the target oligomers existed as transient species. Considerable activity was manifested at agent concentrations as low as 100 nM.

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Acknowledgments

This work was supported by the Korea Science and Engineering Foundation through the National Research Laboratory Program (No. M10500000001-06J0000-00110) funded by the Ministry of Science and Technology.

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Authors and Affiliations

  1. Department of Chemistry, Seoul National University, Seoul, 151-747, South Korea

    Junghun Suh, Woo Suk Chei, Tae Yeon Lee, Min Gyum Kim, Sang Ho Yoo, Keunhong Jeong & Jae Young Ahn

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  1. Junghun Suh
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  2. Woo Suk Chei
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Correspondence to Junghun Suh.

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Suh, J., Chei, W.S., Lee, T.Y. et al. Cleavage agents for soluble oligomers of human islet amyloid polypeptide. J Biol Inorg Chem 13, 693–701 (2008). https://doi.org/10.1007/s00775-008-0354-y

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  • DOI: https://doi.org/10.1007/s00775-008-0354-y

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