HALOGENATED SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 93

The formation of Cys dimers has also been suggested under acidic condi-
tions [93].
A recent study showed HOSCN attacked the Cys residues present in
protein tyrosine phosphatases (PTPs), causing a loss of PTP activity for the
isolated enzyme, in cell lysates and intact J774A.1 macrophage-like cells [5].
This ultimately resulted in altered mitogen-activated protein kinase (MAPK)
signaling. The HOSCN may also induce the inactivation of thiol-dependent
enzymes in which sulfenyl thiocynate and sufenic acid were the intermediates
[94]. Overall, HOSCN-mediated oxidation of thiol may play a role as an
important mediator of inflammation-induced modulation of cellular signaling
and oxidative damage. The role of HOSCN would depend on both the cellular
environment and the specific cell type [94, 95]. Further studies are needed to
fully understand how HOSCN interacts with cellular membranes and the
specific cellular targets.

3.2 HALAMINES

Halamines (RNHCl and RHBr) are key intermediates, formed from the reac-
tions of HOCl and HOBr, respectively, which may also have oxidizing power
to induce further reactions in biological systems [16, 17, 71]. The reactions of
halamines with nitrogenous compounds are also of interest as a disinfection
process in water [32, 96-98]. Halamines undergo different pathways in their
reactions such as hydrolysis, halogen transfer, and one-electron reduction.
These pathways are described below.

3.2.1 Hydrolysis of Halamines

Chloramines, located at the α-amino site, decompose to unstable intermedi-
ates imines, which, upon hydrolysis, form aldehydes and ammonia (Eqs. 3.14
and 3.15) [49, 99, 100]:

R-CH -NHCl R-CH NH HCl
2

→ = + (3.14)

R-CH NH H O R-CH O NH = + → = +

3 .

(3.15)

2

Chloramines of the N-terminus of small peptides have shown to form alde-
hydes [101]. Carbonyls have been detected in the treatment of various proteins
with HOCl [102-106]. The resulting ammonia may react with excess HOCl to
yield NH 2 Cl. Aldehydes may also undergo further reactions with free amino
groups of proteins (e.g., lys side chains) to produce a Schiff base [100, 107].
Reactions of N -bromosuccinamide with amino acids and their peptides
have been studied in the acidic medium [108-110]. The rates of peptides are
lower than those of free amino acids. The roles of the function group and
hydrophobicity were suggested. For example, N -bromosuccinamide oxidized
Val-Pro at a faster rate than the less hydrophobic dipeptides, Ala-Pro and