Effect of side chains on competing pathways for beta-scission reactions of peptide-backbone alkoxyl radicals

Geoffrey P F Wood; Christopher J Easton; Arvi Rauk; Michael Jonathan Davies; Leo Radom

doi:10.1021/jp062916j

Effect of side chains on competing pathways for beta-scission reactions of peptide-backbone alkoxyl radicals

Geoffrey P F Wood, Christopher J Easton, Arvi Rauk, Michael Jonathan Davies, Leo Radom

19 Citationer (Scopus)

Abstract

High-level quantum chemistry calculations have been carried out to investigate beta-scission reactions of alkoxyl radicals located at the alpha-carbon of a peptide backbone. This type of alkoxyl radical may undergo three possible beta-scission reactions, namely C-C beta-scission of the backbone, C-N beta-scission of the backbone, and C-R beta-scission of the side chain. We find that the rates for the C-C beta-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 beta-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 beta-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 beta-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 < Gln approximately Leu approximately Met approximately Lys approximately Arg < Asp approximately Ile approximately Asn approximately Val < Ser approximately Thr approximately Cys < Phe approximately Tyr approximately His approximately Trp. We predict that for side-chain C-R beta-scission reactions to effectively compete with the backbone C-C beta-scission reactions, the side-chain fragment radicals would generally need an RSE greater than approximately 30 kJ mol(-1). Thus, the residues that may lead to competitive side-chain beta-scission reactions are Ser, Thr, Cys, Phe, Tyr, His, and Trp.

Originalsprog	Engelsk
Tidsskrift	Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory
Vol/bind	110
Udgave nummer	34
Sider (fra-til)	10316-23
Antal sider	8
ISSN	1089-5639
DOI	https://doi.org/10.1021/jp062916j
Status	Udgivet - 31 aug. 2006
Udgivet eksternt	Ja

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10.1021/jp062916j

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Effect of side chains on competing pathways for beta-scission reactions of peptide-backbone alkoxyl radicals. / Wood, Geoffrey P F; Easton, Christopher J; Rauk, Arvi et al.

I: Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory, Bind 110, Nr. 34, 31.08.2006, s. 10316-23.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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title = "Effect of side chains on competing pathways for beta-scission reactions of peptide-backbone alkoxyl radicals",

abstract = "High-level quantum chemistry calculations have been carried out to investigate beta-scission reactions of alkoxyl radicals located at the alpha-carbon of a peptide backbone. This type of alkoxyl radical may undergo three possible beta-scission reactions, namely C-C beta-scission of the backbone, C-N beta-scission of the backbone, and C-R beta-scission of the side chain. We find that the rates for the C-C beta-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 beta-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 beta-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 beta-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 < Gln approximately Leu approximately Met approximately Lys approximately Arg < Asp approximately Ile approximately Asn approximately Val < Ser approximately Thr approximately Cys < Phe approximately Tyr approximately His approximately Trp. We predict that for side-chain C-R beta-scission reactions to effectively compete with the backbone C-C beta-scission reactions, the side-chain fragment radicals would generally need an RSE greater than approximately 30 kJ mol(-1). Thus, the residues that may lead to competitive side-chain beta-scission reactions are Ser, Thr, Cys, Phe, Tyr, His, and Trp.",

keywords = "Alcohols, Models, Chemical, Molecular Structure, Peptides, Quantum Theory",

author = "Wood, {Geoffrey P F} and Easton, {Christopher J} and Arvi Rauk and Davies, {Michael Jonathan} and Leo Radom",

year = "2006",

month = aug,

day = "31",

doi = "10.1021/jp062916j",

language = "English",

volume = "110",

pages = "10316--23",

journal = "Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory",

issn = "1089-5639",

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number = "34",

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TY - JOUR

T1 - Effect of side chains on competing pathways for beta-scission reactions of peptide-backbone alkoxyl radicals

AU - Wood, Geoffrey P F

AU - Easton, Christopher J

AU - Rauk, Arvi

AU - Davies, Michael Jonathan

AU - Radom, Leo

PY - 2006/8/31

Y1 - 2006/8/31

N2 - High-level quantum chemistry calculations have been carried out to investigate beta-scission reactions of alkoxyl radicals located at the alpha-carbon of a peptide backbone. This type of alkoxyl radical may undergo three possible beta-scission reactions, namely C-C beta-scission of the backbone, C-N beta-scission of the backbone, and C-R beta-scission of the side chain. We find that the rates for the C-C beta-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 beta-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 beta-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 beta-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 < Gln approximately Leu approximately Met approximately Lys approximately Arg < Asp approximately Ile approximately Asn approximately Val < Ser approximately Thr approximately Cys < Phe approximately Tyr approximately His approximately Trp. We predict that for side-chain C-R beta-scission reactions to effectively compete with the backbone C-C beta-scission reactions, the side-chain fragment radicals would generally need an RSE greater than approximately 30 kJ mol(-1). Thus, the residues that may lead to competitive side-chain beta-scission reactions are Ser, Thr, Cys, Phe, Tyr, His, and Trp.

AB - High-level quantum chemistry calculations have been carried out to investigate beta-scission reactions of alkoxyl radicals located at the alpha-carbon of a peptide backbone. This type of alkoxyl radical may undergo three possible beta-scission reactions, namely C-C beta-scission of the backbone, C-N beta-scission of the backbone, and C-R beta-scission of the side chain. We find that the rates for the C-C beta-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 beta-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 beta-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 beta-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 < Gln approximately Leu approximately Met approximately Lys approximately Arg < Asp approximately Ile approximately Asn approximately Val < Ser approximately Thr approximately Cys < Phe approximately Tyr approximately His approximately Trp. We predict that for side-chain C-R beta-scission reactions to effectively compete with the backbone C-C beta-scission reactions, the side-chain fragment radicals would generally need an RSE greater than approximately 30 kJ mol(-1). Thus, the residues that may lead to competitive side-chain beta-scission reactions are Ser, Thr, Cys, Phe, Tyr, His, and Trp.

KW - Alcohols

KW - Models, Chemical

KW - Molecular Structure

KW - Peptides

KW - Quantum Theory

U2 - 10.1021/jp062916j

DO - 10.1021/jp062916j

M3 - Journal article

C2 - 16928124

SN - 1089-5639

VL - 110

SP - 10316

EP - 10323

JO - Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory

JF - Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory

IS - 34

ER -

Effect of side chains on competing pathways for beta-scission reactions of peptide-backbone alkoxyl radicals

Abstract

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