Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis.
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).
Brouwer
Arwin J
AJ
Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, NL-3508 TB Utrecht, The Netherlands.
Elgersma
Ronald C
RC
Jagodzinska
Monika
M
Rijkers
Dirk T S
DT
Liskamp
Rob M J
RM
D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry*; D000682:Amyloid / Q000138:chemical synthesis*; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010446:Peptide Fragments / Q000138:chemical synthesis*; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry*
D000475:Alkenes; D000682:Amyloid; D004151:Dipeptides; D010446:Peptide Fragments; D013449:Sulfonamides; C117453:amylin (20-29)