TY - JOUR
T1 - Preventing protein oxidation with sugars
T2 - scavenging of hypohalous acids by 5-selenopyranose and 4-selenofuranose derivatives
AU - Storkey, Corin
AU - Pattison, David I
AU - White, Jonathan M
AU - Schiesser, Carl H
AU - Davies, Michael Jonathan
PY - 2012/11/19
Y1 - 2012/11/19
N2 - Heme peroxidases including myeloperoxidase (MPO) are released at sites of inflammation by activated leukocytes. MPO generates hypohalous acids (HOX, X = Cl, Br, SCN) from H(2)O(2); these oxidants are bactericidal and are key components of the inflammatory response. However, excessive, misplaced or mistimed production can result in host tissue damage, with this implicated in multiple inflammatory diseases. We report here methods for the conversion of simple monosaccharide sugars into selenium- and sulfur-containing species that may act as potent water-soluble scavengers of HOX. Competition kinetic studies show that the seleno species react with HOCl with rate constants in the range 0.8-1.0 × 10(8) M(-1) s(-1), only marginally slower than those for the most susceptible biological targets including the endogenous antioxidant, glutathione. The rate constants for the corresponding sulfur-sugars are considerably slower (1.4-1.9 × 10(6) M(-1) s(-1)). Rate constants for reaction of the seleno-sugars with HOBr are ~8 times lower than those for HOCl (1.0-1.5 × 10(7) M(-1) s(-1)). These values show little variation with differing sugar structures. Reaction with HOSCN is slower (~10(2) M(-1) s(-1)). The seleno-sugars decreased the extent of HOCl-mediated oxidation of Met, His, Trp, Lys, and Tyr residues, and 3-chlorotyrosine formation, on both isolated bovine serum albumin and human plasma proteins, at concentrations as low as 50 μM. These studies demonstrate that novel selenium (and to a lesser extent, sulfur) derivatives of monosaccharides could be potent modulators of peroxidase-mediated damage at sites of acute and chronic inflammation, and in multiple human pathologies.
AB - Heme peroxidases including myeloperoxidase (MPO) are released at sites of inflammation by activated leukocytes. MPO generates hypohalous acids (HOX, X = Cl, Br, SCN) from H(2)O(2); these oxidants are bactericidal and are key components of the inflammatory response. However, excessive, misplaced or mistimed production can result in host tissue damage, with this implicated in multiple inflammatory diseases. We report here methods for the conversion of simple monosaccharide sugars into selenium- and sulfur-containing species that may act as potent water-soluble scavengers of HOX. Competition kinetic studies show that the seleno species react with HOCl with rate constants in the range 0.8-1.0 × 10(8) M(-1) s(-1), only marginally slower than those for the most susceptible biological targets including the endogenous antioxidant, glutathione. The rate constants for the corresponding sulfur-sugars are considerably slower (1.4-1.9 × 10(6) M(-1) s(-1)). Rate constants for reaction of the seleno-sugars with HOBr are ~8 times lower than those for HOCl (1.0-1.5 × 10(7) M(-1) s(-1)). These values show little variation with differing sugar structures. Reaction with HOSCN is slower (~10(2) M(-1) s(-1)). The seleno-sugars decreased the extent of HOCl-mediated oxidation of Met, His, Trp, Lys, and Tyr residues, and 3-chlorotyrosine formation, on both isolated bovine serum albumin and human plasma proteins, at concentrations as low as 50 μM. These studies demonstrate that novel selenium (and to a lesser extent, sulfur) derivatives of monosaccharides could be potent modulators of peroxidase-mediated damage at sites of acute and chronic inflammation, and in multiple human pathologies.
KW - Free Radical Scavengers
KW - Hypochlorous Acid
KW - Molecular Structure
KW - Monosaccharides
KW - Organoselenium Compounds
KW - Oxidation-Reduction
KW - Peroxidase
KW - Thiocyanates
U2 - 10.1021/tx3003593
DO - 10.1021/tx3003593
M3 - Journal article
C2 - 23075063
SN - 0893-228X
VL - 25
SP - 2589
EP - 2599
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 11
ER -
