Aggregation and conformational studies on a pentapeptide derivative.
Most of the disease causing proteins such as beta amyloid, amylin, and huntingtin protein, which are natively disordered, readily form fibrils consisting of beta-sheet polymers. Though all amyloid fibrils are made up of beta-sheet polymers, not all peptides with predominant beta-sheet content in the native state develop into amyloid fibrils. We hypothesize that stable amyloid like fibril formation may require mixture of different conformational states in the peptide. We have tested this hypothesis on amyloid forming peptide namely HCl(Ile)(5)NH(CH(2)CH(2)O)(3)CH(3) (I). We show peptide I, has propensity to form self-assembled structures of beta-sheets in aqueous solutions. When incubated over a period of time in aqueous buffer, I self assembled into beta sheet like structures with diameters ranging from 30 to 60 A that bind with amyloidophilic dyes like Congo red and Thioflavin T. Interestingly peptide I developed into unstable fibrils after prolonged aging at higher concentration in contrast with the general mature fibril-forming propensity of various amyloid petides known to date.
Sambasivam
Dhandayuthapani
D
Bioorganic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, India.
Liu
Corey W
CW
Jayaraman
Murali
M
Malar
E J Padma
EJ
Rajadas
Jayakumar
J
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D052160:Benzothiazoles; D057927:Hydrophobic and Hydrophilic Interactions; D007532:Isoleucine / Q000737:chemistry / Q000378:metabolism; D008027:Light; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012542:Scattering, Radiation; D012997:Solvents / Q000494:pharmacology; D013057:Spectrum Analysis; D013844:Thiazoles / Q000378:metabolism; D014867:Water / Q000494:pharmacology
D000682:Amyloid; D052160:Benzothiazoles; D009842:Oligopeptides; D011108:Polymers; D012997:Solvents; D013844:Thiazoles; D007532:Isoleucine; D014867:Water; C009462:thioflavin T