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Diagnostic cyclisation reactions which follow phosphate transfer to carboxylate anion centres for energised [M–H]– anions of pTyr-containing peptides
Journal article   Peer reviewed

Diagnostic cyclisation reactions which follow phosphate transfer to carboxylate anion centres for energised [M–H]– anions of pTyr-containing peptides

T T Nha Tran, Tianfang Wang, S Hack and J H Bowie
Rapid Communications in Mass Spectrometry, Vol.25(17), pp.2489-2499
2011
url
https://doi.org/10.1002/rcm.5150View
Published Version

Abstract

The low-energy negative ion phosphoTyr to C-terminal -CO2PO3H2 rearrangement occurs for energised peptide [M-H]- anions even when there are seven amino acid residues between the pTyr and C-terminal amino acid residues. The rearranged C-terminal -CO2PO2H(O-) group effects characteristic Sni cyclisation/cleavage reactions. The most pronounced of these involves the electrophilic central backbone carbon of the penultimate amino acid residue. This reaction is aided by the intermediacy of an H-bonded intermediate in which the nucleophilic and electrophilic reaction centres are held in proximity in order for the Sni cyclisation/cleavage to proceed. The Δgreaction is +184 kJ mol-1 with the barrier to the Sni transition state being +240 kJ mol-1 at the HF/6-31 + G(d)//AM1 level of theory. A similar phosphate rearrangement from pTyr to side chain CO2- (of Asp or Glu) may also occur for energised peptide [M-H]- anions. The reaction is favourable: Δgreaction is -44 kJ mol-1 with a maximum barrier of +21 kJ mol-1 (to the initial transition state) when Asp and Tyr are adjacent. The rearranged species R1-Tyr-NHCH(CH2CO2PO3H-)COR2 (R1 = CHO; R2 = OCH3) may undergo an Sni six-centred cyclisation/cleavage reaction to form the product anion R1-Tyr(NH-). This process has a high energy requirement [Δgreaction= +224 kJ mol-1, with the barrier to the Sni transition state being +299 kJ mol-1].

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