Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis
Publication date
2008-01-01
Authors
Brouwer, Arwin J
Elgersma, Ronald C.
Jagodzinska, Monika
Rijkers, D.T.S.
Liskamp, Rob M.J.
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Article
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Abstract
The synthesis of a new peptidomimetic structure, the alkene dipeptidosulfonamide isostere, is described. The synthesis is based on a cross metathesis reaction between two allylic building blocks, both in solution and on the solid phase. This method was also applicable to the solid phase synthesis of alkene dipeptide isosteres. Derivatives of amylin(20-29) containing the alkene dipeptidosulfonamide isostere as well as the alkene dipeptide isostere were successfully synthesized using the solid phase cross metathesis method. Investigation of relations between structure and fibril formation of these amylin(20-29) derivatives showed retardation of fibril formation and altered secondary structures, compared to native amylin(20-29). © 2007 Elsevier Ltd. All rights reserved.
Keywords
Alkenedipeptide isosteres, Alkenedipeptidosulfonamide isosteres, Amyloid, Peptidomimetics, Solid phase cross metathesis, alkene, amylin, dipeptide, dipeptidosulfonamide, sulfonamide, unclassified drug, article, chemical structure, circular dichroism, electrospray mass spectrometry, enzymatic degradation, fiber, peptide synthesis, solid phase synthesis, transmission electron microscopy, Wittig reaction
Citation
Brouwer, A J, Elgersma, R C, Jagodzinska, M, Rijkers, D T S & Liskamp, R M J 2008, 'Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis', Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 1, pp. 78-84. https://doi.org/10.1016/j.bmcl.2007.11.009