Chemistry Reference
In-Depth Information
RSR CO
•
−
→
RSR
•+
+
CO
2
−
.
(5.14)
3
3
The increased reactivity of cysteinyl-dopa-melanin compared to dopa-
melanin with
CO
•−
(Table 5.2) is suggested to relate to the higher reactivity of
the thiol molecule than the amine group. The reaction of glutathione (gSH)
by
CO
•−
in alkaline solution (
k
= 7.1 × 10
8
/M/s) produced only the sulfur-
centered gS
•
(gSSg
•−
) radical [56].
The reactivity of
CO
•−
with aromatic amino acids (Trp, Tyr, and His) was
∼10
8
/M/s. A study of
CO
•−
with numerous tryptophan derivatives proposed an
interaction of
CO
•−
with the aromatic system in the reaction mechanism [54, 63].
In a biological environment, Trp and Tyr may likely be the target for
CO
•−
. An
example is the oxidative modification of Trp-32 in the peptide region (31-36) of
hSOd1 to
N
-formylkynurenine (NFK)- and kynurenine (KyN)-containing
peptides in the presence of
SOD- /H O /HCO
−
or UV photolysis of a Co
complex [64]. Based on electron spin resonance (ESR) spin trapping measure-
ments as well as liquid chromatography-mass spectrometry (LC/MS) evidences,
a mechanism shown in Figure 5.6 was proposed [64]. Initially,
CO
•−
forms a
tryptophanyl radical intermediate, which then causes posttranslational modifi-
cation of Trp-32 to NFK and KyN (Fig. 5.6).
1
2
2
3
O
O
NH
2
NH
2
COOH
COOH
NHCHO
NH
2
NFK(+32)
KYN(+4)
O
2
NH
2
NH
2
COOH
COOH
•
CO
3
-•
N
N
Trp
Trp radical
DBNBS
H
3
N
+
COO
-
CH
Br
O
2
CH
2
O
3
-
S
N
NH
2
O
•
N
Br
COOH
O
N
H
Oxo-tryptophan(+16)
Figure 5.6.
Proposed reaction pathway for oxidation modification of tryptophan by
CO
•−
. N-Formylkynurenine is presumably formed from the tryptophanyl peroxy radical.
The molecular weight of NFK is 32 mass units heavier than the parent peptide residue.
decarboxylation (-CO) of NFK yield a product containing kynurenine that is 4 mass
units heavier. dBNBS, 3,5-dibromo-4-nitrosobenzenesulfonic acid (redrawn from
Zhang et al. [64] with the permission of Elsevier Inc.).
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