Journal article
A cyclic peptide inhibitor of ApoC-II peptide fibril formation: Mechanistic insight from NMR and molecular dynamics analysis
MDW Griffin, L Yeung, A Hung, N Todorova, YF Mok, JA Karas, PR Gooley, I Yarovsky, GJ Howlett
Journal of Molecular Biology | Published : 2012
Abstract
The misfolding and aggregation of proteins to form amyloid fibrils is a characteristic feature of several common age-related diseases. Agents that directly inhibit formation of amyloid fibrils represent one approach to combating these diseases. We have investigated the potential of a cyclic peptide to inhibit fibril formation by fibrillogenic peptides from human apolipoprotein C-II (apoC-II). Cyc[60-70] was formed by disulfide cross-linking of cysteine residues added to the termini of the fibrillogenic peptide comprising apoC-II residues 60-70. This cyclic peptide did not self-associate into fibrils. However, substoichiometric concentrations of cyc[60-70] significantly delayed fibril formati..
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Awarded by Australian Research Council
Funding Acknowledgements
This research was supported under the Australian Research Council's Discovery Projects funding scheme (project number DP0984565). M.D.W.G. is the recipient of an Australian Research Council Post Doctoral Fellowship (project number DP110103528). The authors would like to thank Dr Katrina Binger for advice on A beta preparation, and the Australian National Computational Infrastructure and Victorian Partnership for Advanced Computing for providing computational resources.