Backbone-modified amylin derivatives: implications for amyloid inhibitor design and as template for self-assembling bionanomaterials.
This report reviews our approach to the design, synthesis and structural/morphological analysis of backbone-modified amylin(20-29) derivatives. Depending on the position in the peptide backbone and the type of amide bond isostere/modification, the amylin(20-29) peptides behave either as inhibitors of amyloid fibril formation, which are able to retard amyloid formation of native amylin(20-29), or as templates for the formation of self-assembled supramolecular structures. Molecular fine-tuning of the hydrogen-bond accepting/donating properties allows the control over the morphology of the supramolecular aggregation motifs such as helical ribbons and tapes, ribbons progressing to closed peptide nanotubes, (twisted) lamellar sheets or amyloid fibrils.
Elgersma
Ronald C
RC
Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, The Netherlands.
Posthuma
George
G
Rijkers
Dirk T S
DT
Liskamp
Rob M J
RM
D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D049329:Nanostructures; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure
D000682:Amyloid; D010446:Peptide Fragments; C117453:amylin (20-29)