Premium
Diagnostic cyclisation reactions which follow phosphate transfer to carboxylate anion centres for energised [M–H] – anions of pTyr‐containing peptides
Author(s) -
Tran T. T. Nha,
Wang Tianfang,
Hack Sandra,
Bowie John H.
Publication year - 2011
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.5150
Subject(s) - chemistry , electrophile , nucleophile , cleavage (geology) , stereochemistry , medicinal chemistry , transition state , peptide , ion , carboxylate , catalysis , organic chemistry , geotechnical engineering , fracture (geology) , engineering , biochemistry
The low‐energy negative ion phosphoTyr to C‐terminal ‐CO 2 PO 3 H 2 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 ‐CO 2 PO 2 H(O – ) group effects characteristic S N i 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 S N i cyclisation/cleavage to proceed. The ΔG reaction is +184 kJ mol −1 with the barrier to the S N i 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 CO 2 – (of Asp or Glu) may also occur for energised peptide [M–H] – anions. The reaction is favourable: ΔG reaction 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 R 1 ‐Tyr‐NHCH(CH 2 CO 2 PO 3 H – )COR 2 (R 1 = CHO; R 2 = OCH 3 ) may undergo an S N i six‐centred cyclisation/cleavage reaction to form the product anion R 1 ‐Tyr(NH – ). This process has a high energy requirement [ΔG reaction = +224 kJ mol −1 , with the barrier to the S N i transition state being +299 kJ mol −1 ]. Copyright © 2011 John Wiley & Sons, Ltd.