Solid phase synthesis of four analogs of amyloid-β(9-16) peptide: MS and FT-IR characterization

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia and one of its major neuropathological features is the extracellular deposition of fibrils composed of amyloid-β peptides (Aβ). Our investigation started with a small fragment of Aβ, namely the amyloid Aβ(9-16) peptide (9GYEVHHQK16). Here, we report on the synthesis of four new peptides obtained by replacing with glycine or phenylalanine some amino acid residues in the sequence of the above-mentioned Aβ(9-16) peptide, in order to use them to study the oligomerization and fibrillation processes in the presence of metal ions. The following peptides were synthesized by Fmoc/t-butyl solid-phase synthesis (SPPS) strategy: Aβ(9-16) (9GYEVHHQK16), Aβ(9-16)G (9G10GEVHHQK16), Aβ(9-16)F (9G10FEVHHQK16), Aβ(9-16)GG (9G10YEV13G14GQK16) and Aβ(9-16)GGG (9G10GEV13G14GQK16). The newly synthesized peptides were purified by RP-HPLC and characterized by MALDI-TOF mass spectrometry and Fourier transform infrared spectroscopy (FT-IR) as well as, theoretically, using the GPMAW software. Mass spectrometric spectra confirmed the successful synthesis of the desired peptides, while the hydrophobicity parameter, simulated with the GPMAW software, was shown to be dependent on the structure of each peptide. Infrared spectroscopy showed that the conformation of peptides differs from a peptide to another. Such analogs of Aβ(9-16) peptide fragment are supposed to be of interest in searching the role played by certain amino acids in AD aetiology and, in general, in neurodegeneration.