Abstract
Islet amyloid polypeptide (IAPP) is a hormone cosecreted with insulin. IAPP proceeds through a series of conformational changes from random coil to β-sheet via transient α-helical intermediates. An unknown subset of these events are associated with seemingly disparate gains of function, including catalysis of self-assembly, membrane penetration, loss of membrane integrity, mitochondrial localization, and finally, cytotoxicity, a central component of diabetic pathology. A series of small molecule, α-helical mimetics, oligopyridylamides, was previously shown to target the membrane-bound α-helical oligomeric intermediates of IAPP. In this study, we develop an improved, microwave-assisted synthesis of oligopyridylamides. A series of designed tripyridylamides demonstrate that lipid-catalyzed self-assembly of IAPP can be deliberately targeted. In addition, these molecules affect IAPP-induced leakage of synthetic liposomes and cellular toxicity in insulin-secreting cells. The tripyridylamides inhibit these processes with identical rank orders of effectiveness. This indicates a common molecular basis for the disparate set of observed effects of IAPP.
References
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Apr 19, 2003·Science·Rakez KayedCharles G Glabe
Mar 15, 2005·Angewandte Chemie·Hang YinAndrew D Hamilton
May 4, 2007·Diabetes·Chang-jiang HuangPeter C Butler
Aug 4, 2009·Journal of Molecular Biology·Jessica A WilliamsonAndrew D Miranker
Sep 26, 2009·Chemistry & Biology·James A HebdaAndrew D Miranker
Sep 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Leslie S WolfeYong Xiong
Oct 7, 2010·Biophysical Journal·Elizabeth R Middleton, Elizabeth Rhoades
Apr 16, 2011·Journal of the American Chemical Society·Eva SevcsikElizabeth Rhoades
May 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nicholas B LastAndrew D Miranker
Dec 21, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mazin Magzoub, Andrew D Miranker
Mar 10, 2012·Science·Arthur LaganowskyDavid Eisenberg
Sep 7, 2012·Diabetes, Obesity & Metabolism·M BraunP Rorsman
Apr 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nicholas B Last, Andrew D Miranker
Nov 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ping CaoDaniel P Raleigh
Jul 22, 2014·Protein Science : a Publication of the Protein Society·James A HebdaAndrew D Miranker
Citations
Apr 12, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Ann JunghansIzabela Stroe
May 13, 2015·Biochemistry·Abhinav NathAndrew D Miranker
Jul 1, 2016·Journal of Medicinal Chemistry·Ranganath GopalakrishnanEric Valeur
Mar 9, 2017·Journal of the American Chemical Society·Sunil Kumar, Andrew D Hamilton
Apr 16, 2016·Chemical Communications : Chem Comm·Sunil KumarAndrew D Miranker
Apr 30, 2017·Chemical Science·Hayden PeacockAndrew D Hamilton
Aug 16, 2017·Journal of Molecular Endocrinology·Daniel RaleighAnne Clark
Apr 26, 2016·Nature Communications·Sunil KumarAndrew D Miranker
Mar 3, 2019·Chemistry : a European Journal·Debabrata MaityAndrew D Hamilton
Aug 19, 2015·The Journal of Biological Chemistry·Natalie C KegulianRalf Langen
Oct 7, 2015·Angewandte Chemie·Carole Anne De CarufelSteve Bourgault
Jan 26, 2016·Chembiochem : a European Journal of Chemical Biology·Michal JewginskiCameron David Mackereth
May 30, 2017·Chemical Science·Xiaobo HuIvan Huc
Jan 6, 2018·Organic & Biomolecular Chemistry·Sunil KumarAndrew D Hamilton
Oct 21, 2016·Chembiochem : a European Journal of Chemical Biology·Pradeep K MandalIvan Huc
Jan 12, 2021·Chemical Reviews·Danilo MilardiAyyalusamy Ramamoorthy
Jan 12, 2021·European Journal of Medicinal Chemistry·Sergio AlgarRosario González-Muñiz
Jan 23, 2021·Chemistry : a European Journal·Tim SeedorfDanny Solga
Jun 27, 2021·Nature Communications·L PalanikumarMazin Magzoub
Apr 13, 2018·Journal of the American Chemical Society·Sunil KumarAndrew D Hamilton
Nov 6, 2018·Bioconjugate Chemistry·Maëlle ValladeIvan Huc
Jul 7, 2020·Langmuir : the ACS Journal of Surfaces and Colloids·Qiuchen ZhengNoel D Lazo
Oct 24, 2017·Journal of the American Chemical Society·Sunil KumarAndrew D Hamilton
Aug 29, 2019·Journal of the American Chemical Society·Zachary A LevineJoan-Emma Shea
Aug 31, 2021·RSC Chemical Biology·Debabrata MaityAndrew D Hamilton
Oct 13, 2021·Journal of Cellular Physiology·Carine MarmentiniMirian A Kurauti