TY - JOUR
T1 - Effect of side chains on competing pathways for β-scission reactions of peptide-backbone alkoxyl radicals
AU - Wood, Geoffrey P.F.
AU - Easton, Christopher J.
AU - Rauk, Arvi
AU - Davies, Michael J.
AU - Random, Leo
PY - 2006/8/31
Y1 - 2006/8/31
N2 - High-level quantum chemistry calculations have been carried out to investigate β-scission reactions of alkoxyl radicals located at the α-carbon of a peptide backbone. This type of alkoxyl radical may undergo three possible β-scission reactions, namely C-C β-scission of the backbone, C-N β-scission of the backbone, and C-R β-scission of the side chain. We find that the rates for the C-C β-scission reactions are all very fast, with rate constants of the order 10 12 s -1 that are essentially independent of the side chain. The C-N β-scission reactions are all slow, with rate constants that range from 10 -0.7 to 10 -4.5 s -1. The rates of the C-R β-scission reactions depend on the side chain and range from moderately fast (10 7 s -1) to very fast (10 12 s -1) The rates of the C-R β-scission reactions correlate well with the relative stabilities of the resultant side-chain product radicals (R), as reflected in calculated radical stabilization energies (RSEs). The order of stabilities for the side-chain fragment radicals for the natural amino acids is found to be Ala < Glu < Gin ∼ Leu ∼ Met ∼ Lys ∼ Arg < Asp ∼ Ile ∼ Asn ∼ Val < Ser ∼ Thr ∼ Cys < Phe ∼ Tyr ∼ His ∼ Trp. We predict that for side-chain C-R β-scission reactions to effectively compete with the backbone C-C β-scission reactions, the side-chain fragment radicals would generally need an RSE greater than β30 kJ mol -1. Thus, the residues that may lead to competitive side-chain β-scission reactions are Ser, Thr, Cys, Phe, Tyr, His, and Trp.
AB - High-level quantum chemistry calculations have been carried out to investigate β-scission reactions of alkoxyl radicals located at the α-carbon of a peptide backbone. This type of alkoxyl radical may undergo three possible β-scission reactions, namely C-C β-scission of the backbone, C-N β-scission of the backbone, and C-R β-scission of the side chain. We find that the rates for the C-C β-scission reactions are all very fast, with rate constants of the order 10 12 s -1 that are essentially independent of the side chain. The C-N β-scission reactions are all slow, with rate constants that range from 10 -0.7 to 10 -4.5 s -1. The rates of the C-R β-scission reactions depend on the side chain and range from moderately fast (10 7 s -1) to very fast (10 12 s -1) The rates of the C-R β-scission reactions correlate well with the relative stabilities of the resultant side-chain product radicals (R), as reflected in calculated radical stabilization energies (RSEs). The order of stabilities for the side-chain fragment radicals for the natural amino acids is found to be Ala < Glu < Gin ∼ Leu ∼ Met ∼ Lys ∼ Arg < Asp ∼ Ile ∼ Asn ∼ Val < Ser ∼ Thr ∼ Cys < Phe ∼ Tyr ∼ His ∼ Trp. We predict that for side-chain C-R β-scission reactions to effectively compete with the backbone C-C β-scission reactions, the side-chain fragment radicals would generally need an RSE greater than β30 kJ mol -1. Thus, the residues that may lead to competitive side-chain β-scission reactions are Ser, Thr, Cys, Phe, Tyr, His, and Trp.
UR - http://www.scopus.com/inward/record.url?scp=33748774117&partnerID=8YFLogxK
U2 - 10.1021/jp062916j
DO - 10.1021/jp062916j
M3 - Article
SN - 1089-5639
VL - 110
SP - 10316
EP - 10323
JO - Journal of Physical Chemistry A
JF - Journal of Physical Chemistry A
IS - 34
ER -