Exenatide: NMR/CD evaluation of the medium dependence of conformation and aggregation state

Biopolymers
F Michael Hudson, Niels H Andersen

Abstract

Exenatide, synthetic exendin-4, is the first member of the incretin mimetic class of potential therapeutic agents. It has been the subject of extensive clinical trials in people with Type 2 diabetes. Results to date indicate that exenatide decreases postmeal blood glucose concentrations and that this effect is associated with weight loss. Prior NMR studies of exendin-4 utilized 30% trifluoroethanol because this medium affords sharp, high-resolution NMR spectra. These studies defined its three-dimensional structure in this medium. The NMR-derived ensemble included a novel tertiary structure motif that has subsequently been optimized, yielding water-soluble Trp-cage miniproteins. Prior to the present study, the structuring propensities (and aggregation/association state) of exendin-4 in strictly aqueous media had not been established. Studies of exendin-4 and N-terminally truncated analogs of exendin have established that the structuring propensities of these species are highly medium dependent. This study extends knowledge of the medium dependence of exendin structure to DMSO-water mixtures and to aqueous media mimicking the formulation conditions for this investigational drug. Exenatide retains a substantial helical propensity ...Continue Reading

References

Dec 9, 1996·FEBS Letters·N H AndersenK S Prickett
Sep 23, 1997·Protein Science : a Publication of the Protein Society·N H Andersen, H Tong
Dec 12, 2001·Bioorganic & Medicinal Chemistry·Niels H AndersenKathryn S Prickett
Apr 30, 2002·Nature Structural Biology·Jonathan W NeidighNiels H Andersen
Oct 22, 2002·Biopolymers·Jonathan W Neidigh, Niels H Andersen
Oct 31, 2002·Journal of the American Chemical Society·Linlin QiuStephen J Hagen
Jun 10, 2004·Journal of the American Chemical Society·R Matthew FesinmeyerNiels H Andersen

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Citations

Sep 3, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Rongcai LiangYouxin Li
Jan 22, 2008·Protein Engineering, Design & Selection : PEDS·Bipasha BaruaNiels H Andersen
Jul 15, 2009·Protein Engineering, Design & Selection : PEDS·John R CortNiels H Andersen
Jul 27, 2010·Analytical and Bioanalytical Chemistry·Carlo BertucciAngela De Simone
Feb 20, 2014·Pharmaceutical Research·Rongcai LiangYouxin Li
Jul 23, 2013·International Journal of Pharmaceutics·Rongcai LiangYouxin Li
Mar 19, 2008·Biochemical and Biophysical Research Communications·Manish V BaisKantaraja Chindera
Dec 1, 2012·Annals of the New York Academy of Sciences·Chris HollowayDaan J A Crommelin
May 16, 2014·Biochemistry·Petra RovóAndrás Perczel
Apr 28, 2017·Journal of Medicinal Chemistry·Andreas EversMichael Wagner
Jul 16, 2019·Journal of Pharmaceutical Sciences·John S PhiloTsutomu Arakawa
May 7, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Michael TullyRainer Haag
Jun 5, 2021·Journal of Pharmaceutical and Biomedical Analysis·Subrata H MishraKevin L Carrick
Aug 29, 2021·Pharmaceutics·Alexander BenetAnna Schwendeman

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