Aggregation of short synthetic peptides investigation of morphological features amyloidogenicity and cytotoxicity

Abstract

Protein misfolding and subsequent generation of amyloid fibrils are associated with a wide range of diseases e.g. Alzheimerand#8223;s, Huntingtonand#8223;s, Parkinsonand#8223;s, type II diabetes, cystic fibrosis, and many others. Till date more than two dozen different proteins have been identified which are associated with the formation of amyloid. Although in each case the proteins have unique sequence, structure and function, but in the amyloid state they exhibit both structural and morphological resemblance. In amyloid state, proteins adopt and#946;-sheet conformation and assemble into nanofibrillar aggregates having diameter ~20 nm and several micrometers in length. The most important property of amyloid fibrils is its robust mechanical strength which is comparable to steel and silk. They are resistant to harsh physical condition like heat, wide ranges of pH, proteases etc. Moreover, these nanofibrils of different origins exhibit similar biophysical characteristics. It can bind with congo red (CR) and CR-peptide (amyloid) conjugate shows enhancement in molar absorption as well as characteristic birefringence under cross polarized light. Amyloid can also form stable conjugate with thioflavine t (ThT) which shows enhanced emission at ~ 482 nm upon excitation at 450 nm. There are various polypeptides, proteins and small synthetic peptides which do not bear any sequence similarity with each other or with any pathogenic amyloid forming proteins, but can form nano-fibrillar aggregates having all characteristics properties of amyloid. This reinforces that amyloid formation is a generic property of the polypeptides chain. Recent studies have revealed that amyloid states of protein are also capable of performing various native biological functions in the host organism and are thus termed as functional amyloids. But the solubility of amyloids in aqueous medium is very poor. Moreover they are noncrystalline in nature. Till date, the intricacies of amyloid fibrillogenesis process are not clearly understood mainly due to its noncrystalinity and poor s