Synthesis and testing of peptides for anti-prion activity.
Creutzfeldt-Jakob disease (CJD) is one of the fatal transmissible spongiform encephalopathies for which there is no known cure. The disease is associated with an abnormally folded prion protein, PrP-res, which is thought to form due to interaction between normal prion PrP(C) and PrP-res. Small peptides were designed to prevent this interaction. A structure-activity relationship is described for a series of peptides which were synthesised and tested for their activity against two prion disease model assays, an in vitro cellular assay and an in vitro anti-aggregation polymerisation assay. A number of peptides were found to be active at levels of 100microM. New libraries were synthesised in order to concentrate on discovering new, shorter peptides which could be leads for developing peptidomimetics.
Sellarajah
Shane
S
Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK.
Boussard
Cyrille
C
Lekishvili
Tamuna
T
Brown
David R
DR
Gilbert
Ian H
IH
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D017124:Conserved Sequence; D006224:Cricetinae; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011489:Protein Denaturation / Q000187:drug effects; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
D010455:Peptides; D011328:Prions