Investigation of peptide size, residue position, neighbor amino acid and side chain effect on macrocyclization of b _n (n = 5-7) ions

摘要

A systematic study was carried out to examine the effects of the side chain, peptide size, residue position, and neighboring amino acid on the macrocyclization of b ions. The work utilized isomeric model peptides YAGFLV-NH _2, AGFLVY-NH _2, GFLVYA-NH _2, FLVYAG-NH _2, LVYAGF-NH _2, VYAGFL-NH _2, which all have the same amino acid sequence in cyclic form. The b _6 ions derived from all these isomeric peptides form the same macrocyclic structure due to the generation of the same amino acid sequence order upon cyclization. Hence, the MS/MS spectra and breakdown graphs of b _6 ions derived from these peptides are similar to each other. However, the relative intensities of the non-direct sequence ions in both the MS/MS spectra and breakdown graphs of the b _6 ions derived from FAYVGL-NH _2, GVYALF-NH _2 and VFYLAG-NH _2 show a different distribution from each other and the first series, even though they are all isomeric peptides. This could be due to the different amino acid sequence order in the cyclic forms of these peptides. It is clearly shown that the neighboring amino acid influences the selective opening of the macrocyclic form. Additionally, XYAGFLV-NH _2 and YAGXFLV-NH _2 (where X = C, D, E, H, K, M, N, P, Q, S, T, and W are amino acid residues) were also studied in order to examine the influence of the peptide size, amino acid side chain, and position on the ring formation and cleavage of macrocyclic b _5, b _6 and b _7 ions. The results have clearly shown that b _6 and b _7 ions have a higher tendency of macrocyclization compared to b _5 ions with the exception of QYAGFLV-NH _2. Additionally, it was observed that selective ring opening is also dependent on the size of the b ions and the position of the amino acid residue. From our study of the macrocyclic b _6 ions of our model peptides, the Q, W, K, and M residues were found to be more favorable eliminations when compared to C, D, E, H, N, P, S, and T. Based on the results, no preferential cleavage order can be specified depending on the nature of amino acid side chain.