Structural highlights
Publication Abstract from PubMed
Aggregation of the islet amyloid polypeptide (IAPP) to form fibrils and oligomers is important in the progression of type 2 diabetes. This article describes X-ray crystallographic and solution-state NMR studies of peptides derived from residues 11-17 of IAPP that assemble to form tetramers. Incorporation of residues 11-17 of IAPP (RLANFLV) into a macrocyclic beta-sheet peptide results in a monomeric peptide that does not self-assemble to form oligomers. Mutation of Arg11 to the uncharged isostere citrulline gives peptide homologues that assemble to form tetramers in both the crystal state and in aqueous solution. The tetramers consist of hydrogen-bonded dimers that sandwich together through hydrophobic interactions. The tetramers share several features with structures reported for IAPP fibrils and demonstrate the importance of hydrogen bonding and hydrophobic interactions in the oligomerization of IAPP-derived peptides.
A Tetramer Derived from Islet Amyloid Polypeptide.,Wang Y, Kreutzer AG, Truex NL, Nowick JS J Org Chem. 2017 Aug 4;82(15):7905-7912. doi: 10.1021/acs.joc.7b01116. Epub 2017 , Jul 14. PMID:28661686[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang Y, Kreutzer AG, Truex NL, Nowick JS. A Tetramer Derived from Islet Amyloid Polypeptide. J Org Chem. 2017 Aug 4;82(15):7905-7912. doi: 10.1021/acs.joc.7b01116. Epub 2017 , Jul 14. PMID:28661686 doi:http://dx.doi.org/10.1021/acs.joc.7b01116
