title: Diagnostic cyclisation reactions which follow phosphate transfer to carboxylate anion centres for energised [M-H]- anions of pTyr-containing peptides.
abstract: 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)].
authors.affiliation: Department of Chemistry, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: T T Nha
authors.initials: TT
authors.lastname: Tran
authors.forename: Tianfang
authors.initials: T
authors.lastname: Wang
authors.forename: Sandra
authors.initials: S
authors.lastname: Hack
authors.forename: John H
authors.initials: JH
authors.lastname: Bowie
mesh_terms: D000838:Anions / Q000737:chemistry / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry; D003500:Cyclization; D013058:Mass Spectrometry; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism; D019000:Phosphotyrosine / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D000838:Anions; D002264:Carboxylic Acids; D010456:Peptides, Cyclic; D019000:Phosphotyrosine