The role of the disulfide bond in amyloid-like fibrillogenesis in a model peptide system.
Three terminally protected short peptides Bis[Boc-D-Leu1-Cys2-OMe] 1, Bis[Boc-Leu1-Cys2-OMe] and Bis[Boc-Val1-Cys2-OMe] 3 exhibit amyloid-like fibrillar morphology. Single crystal X-ray diffraction analysis of peptide 1 clearly demonstrates that it adopts an overall extended backbone molecular conformation that self-assembles to form an intermolecular hydrogen-bonded antiparallel supramolecular beta-sheet structure in crystals. Scanning electron microscopic (SEM) images, transmission electron microscopic (TEM) images and Congo red binding studies vividly demonstrate the amyloid-like fibril formation of peptides 1, 2 and 3. However, after reduction of the disulfide bridge of peptides 1, 2 and 3, three newly generated peptides Boc-D-Leu1-Cys2-OMe 4, Boc-Leu1-Cys2-OMe 5 and Boc-Val1-Cys2-OMe 6 are formed and all of them failed to form any kind of fibril under the same conditions, indicating the important role of the disulfide bond in amyloid-like fibrillogenesis in a peptide model system.
Das
Apurba Kumar
AK
Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India.
Drew
Michael G B
MG
Haldar
Debasish
D
Banerjee
Arindam
A
D000682:Amyloid / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D003553:Cystine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D006860:Hydrogen Bonding; D007930:Leucine / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D014633:Valine / Q000737:chemistry; D014961:X-Ray Diffraction
D000682:Amyloid; D004220:Disulfides; D010455:Peptides; D003553:Cystine; D007930:Leucine; D014633:Valine