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

Abstract

a b s t r a c tA 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.

Specific rearrangement reactions of acetylated lysine containing peptide bn (n = 4–7) ion series

“…The m/z 651 ion was observed as the most abundant fragment ion in the CID-MS 4 mass spectrum, and the further isolation (CID-MS 5 ) of the m/z 651 ion have resulted the same CID mass spectra of b 6 ions derived from permuted isomers of YAGFLV-NH 2 , whose CID mass spectra have been reported from our group previously. [36,37] The CID mass spectrum of m/z 668 fragment from b 7 ion of protonated K Ac YAGFLVG and YAGFLV-NH 2 peptides is given in Fig. 2(a).…”

Gas-phase structures and proton affinities of N-terminal proline containing b2+ ions from protonated model peptides

“…In recent years, Harrison and co-workers reported that middlesized b n + (n ≥ 4) ions undergo macrocyclization followed by ring-opening process in low-energy CID conditions [16,17]. Numerous studies have provided a better understanding of the cyclization chemistry of b ions [18][19][20][21][22][23][24]. It is worth noting here that the presence of proline residue may affect the structure of b 2 + ion.…”

Gas‐phase fragmentation reactions of a7 ions containing a glutamine residue

“…IRMPD studies have provided strong evidence for forming macrocyclic structures in the gas phase 22–24 . Previous studies have been conducted to investigate the influences of different parameters (i.e., peptide length, amino acid type, and side‐chain functionality) on the formation of macrocyclic structures 23,25–33 …”