Mn(III) oxidation of peptides: A mechanistic investigation of kinetic variations in hydrophobic-induced oxidation of tetrapeptides of elastin sequences

Article abstract of DOI:10.1002/kin.20144

Four tetrapeptide analogues of elastin sequences, glycyl-glycyl-alanyl- proline (GGAP), glycyl-glycyl-valyl-proline (GGVP), glycyl-glycyl-isoleucyl- proline (GGIP), and glycyl-glycyl-phenylalanyl-proline (GGFP) were synthesized, based on their increasing order of hydrophobicity, by a classical solution phase method and were characterized. These tetrapeptides (TETPs) were oxidized using Mn(OAc)₃ in 25% acetic acid at 298 K, and the kinetics of the reaction was monitored spectrophotometrically at λ_max == 400 nm. A first-order dependence of rate on each of [Mn(OAc)₃], [OAc ^-], and substrate [TETP], an inverse order dependence on [H ⁺], has been observed. The rate is independent of [Mn(II)]. However, an inverse order dependence on varying the dielectric constant using various percentages (v/v) of acetic acid has also been observed, and but addition of anions such as Cl^- and ClO₄^- has insignificant effect on the rate. Activation parameters have been evaluated using the Arrhenius and Erying plots. The oxidation products were isolated and characterized. Based on the results obtained, a plausible mechanism involving [Mn(OAc)₄]^- has been proposed. An apparent correlation was noted between the rate of oxidation of these TETPs by Mn(III) in the presence of sulfate ions in sulfuric acid medium and Mn(OAc)₃ in the acetic acid medium. The rate of oxidation with Mn(OAc)₃ was observed to be slower than with the former. The rate of oxidation of GGFP was found to be higher than GGIP, GGVP, and GGAP, This may be due to the presence of an aromatic side chain and/or because of the increased hydrophobicity. The overall order of rate of oxidation of TETPs is GGFP > GGIP > GGVP > GGAP, which also represents an increasing order of their hydrophobicity.

Full text of DOI:10.1002/kin.20144

Mn(III) Oxidation of
Peptides: A Mechanistic
Investigation of Kinetic
Variations in
Hydrophobic-Induced
Oxidation of Tetrapeptides
of Elastin Sequences
G. R. SRINIVASA, K. ABIRAJ, A. RAMESHA BABA, D. CHANNE GOWDA
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, India
Received 28 January 2005; accepted 30 August 2005
DOI 10.1002/kin.20144
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: Four tetrapeptide analogues of elastin sequences, glycyl-glycyl-alanyl-proline
(GGAP), glycyl-glycyl-valyl-proline (GGVP), glycyl-glycyl-isoleucyl-proline (GGIP), and glycyl-
glycyl-phenylalanyl-proline (GGFP) were synthesized, based on their increasing order of
hydrophobicity, by a classical solution phase method and were characterized. These tetrapep-
tides (TETPs) were oxidized using Mn(OAc)3 in 25% acetic acid at 298 K, and the kinetics of the
reaction was monitored spectrophotometrically at λmax = 400 nm. A first-order dependence
of rate on each of [Mn(OAc)3], [OAc−], and substrate [TETP], an inverse order dependence on
[H+], has been observed. The rate is independent of [Mn(II)]. However, an inverse order depen-
dence on varying the dielectric constant using various percentages (v/v) of acetic acid has also
−
been observed, and but addition of anions such as Cl− and ClO4 has insignificant effect on
the rate. Activation parameters have been evaluated using the Arrhenius and Erying plots. The
oxidation products were isolated and characterized. Based on the results obtained, a plausible
mechanism involving [Mn(OAc)4]− has been proposed. An apparent correlation was noted
Correspondence to: D. Channe Gowda; e-mail: dcgowda@
yahoo.com.
Contract grant sponsor: Council of Scientific and Industrial
Research, New Delhi, India.
Contract grant sponsor: University Grants Commission,
New Delhi, India.
c
ꢀ
2005 Wiley Periodicals, Inc.

116
SRINIVASA ET AL.
between the rate of oxidation of these TETPs by Mn(III) in the presence of sulfate ions in sulfuric
acid medium and Mn(OAc)3 in the acetic acid medium. The rate of oxidation with Mn(OAc)3
was observed to be slower than with the former. The rate of oxidation of GGFP was found to
be higher than GGIP, GGVP, and GGAP. This may be due to the presence of an aromatic side
chain and/or because of the increased hydrophobicity. The overall order of rate of oxidation
of TETPs is GGFP > GGIP > GGVP > GGAP, which also represents an increasing order of their
hydrophobicity. ꢀ 2005 Wiley Periodicals, Inc. Int J Chem Kinet 38: 115–123, 2006
C
INTRODUCTON
both the absence and the presence of fetal bovine serum
[20]. The degree of cell attachment increased with the
increase of hydrophobicity. Therefore, in particular hy-
drophobicity and hydrophilicity are the two important
phenomena of interest exhibited by peptides and pro-
teins, to understand their behavior in solution, when
they are said to be solute. In this context, interest was
generated to investigate the oxidative behavior of metal
ions toward these analogues of repeating sequences of
elastin.
Reactions of oxidants with biological targets such as
DNA, RNA, cholesterol, lipids, carbohydrates, pro-
teins, and antioxidants play an important role in the
biological processes [1–4]. Such oxidation studies may
throw some light on the mechanism of conversions of
the compounds in the biological systems. However, ox-
idation of proteins is gaining more attention, as they are
the major components of most of the biological sys-
tems. An extensive work has been reported on the ki-
netics of oxidation of proteins and its constituents, with
various metal ions and several other oxidants [5,6]. In
this account, Mn(III) oxidation is of special importance
due to its biological relevance. Mn(III) porphyrins have
been studied as possible models for closely related bi-
ologically significant systems [7]. In recent years, ki-
netics of oxidation of amino acids, its derivatives, pep-
tides, and proteins have been studied using Mn(III) in
different mediums [8–12].
“Elastin” is an important protein, which is respon-
sible for the elasticity of skin, ligaments, and arter-
ies. Elastic protein-based polymers are the polypep-
tides comprising repeating sequences of amino acids,
having their origin in a protein, elastin. The most strik-
ing repeating sequence is poly(VPGVG) or (Val1-Pro2-
Gly3-Val4-Gly5)n or (VPGVG)n, that is so apparent
in the bovine and porcine elastins where n = 11 or
more [13,14]. Another repeat first found in porcine
elastin is a polytetrapeptide-(PTP), poly(VPGG) or
(Val1-Pro2-Gly3-Gly4)n, but this repeat has not been
found to occur with n greater than 2 without substitu-
tion [15]. The monomers, oligomers, and high molecu-
lar weight polymers of these repeats have been synthe-
sized and conformationally characterized [16]. Such
protein-based polymers exhibit the same hierarchical
structure and mimic the parent protein. These polymers
have a number of medical and nonmedical applications
[17,18]. The hydorgel state of poly(GGAP) or (Gly-
Gly-Ala-Pro)n is most extraordinary biocompatible
and nonmutagenic, which is suitable for the controlled
release of drug [19]. The cross-linked polytetrapeptide
matrices based on the repeating amino acid sequences,
Gly-Gly-Ala-Pro, Gly-Gly-Ile-Pro, and Gly-Gly-Val-
Pro were tested for cell adhesion promoting activity in
EXPERIMENTAL
Peptide Synthesis
All amino acids used are of the L-configuration
except glycine. All ter-butyloxycarbonyl (Boc) amino
acid derivatives, 3-ethyl-1(N,N-dimethyl)amino-
propylcarbodiimide (EDCI), 1-hydroxybenzotriazole
(HOBt), and trifluoroacetic acid (TFA) were pur-
chased from Advanced Chem Tech (Louisville, KY).
N-methyl morpholine (NMM) was purchased from
Sigma Chemical Co. (St. Louis, MO). All other
reagents used were of analytical grade. Purity of
the peptides was checked at every step using thin
layer chromatography, carried out on silica gel plates
obtained from Whatman Inc. (developing solvent
system: CHCl3:CH3OH:AcOH, 95:5:3). Further, they
were verified with 1H NMR at least at the tetrapeptide
stage and the final product. The final products were
also subjected to melting point, elemental analysis,
and HPLC amino acid analysis.
The peptides were synthesized by a classical so-
lution phase peptide synthesis by a stepwise ap-
proach. The peptide Boc-Gly-Val-Pro-OBzl and the
TETPs GGAP, GGIP, and GGFP were synthe-
sized as previously described [9,11]. The synthe-
sis and characterization of GGVP are described
here.
Boc-Gly-Gly-Val-Pro-OBzl (I). Boc-Gly-Val-Pro-OBzl
(4.62 g, 10 mmol) was deblocked by stirring for 1.5 h
in 4 N HCl in dioxane (10 mL/g). Excess of HCl
and dioxane was removed under reduced pressure,

Mn(III) OXIDATION OF PEPTIDES
117
plex [Mn(OAc)4]−. The standard reduction potential
Eoꢁ , the oxidizing power of the oxidant Mn(III)/Mn(II),
generally decreases on complexation. The standard re-
dox potential was measured at the specified experi-
mental conditions. These details were reported previ-
ously [24]. The formal redox potential Eoꢁ obtained
at different concentration of acetic acid is 1.160 V
for the pure system, and in the presence other com-
triturated with dry ether, filtered, washed with ether
and dried to give 3.96 g of HCl·H-Gly-Val-Pro-OBzl
(yield 99.62%). To a solution of Boc-Gly-OH (1.75 g,
10 mmol) in DMF (15 mL) cooled in an ice bath
to −15 1◦C, HOBt (1.53 g, 10 mmol) and EDCI
(1.92 g, 10 mmol) were added. After stirring for
20 min, a precooled solution of HCl·H-Gly-Val-Pro-
OBzl and NMM (1.1 mL) in DMF (40 mL) was
added and the mixture was stirred for overnight at
room temperature. The solvent was removed under
reduced pressure, and the residue was taken into
CHCl3. The organic phase was washed sequentially
with 50% saturated NaCl, 5% NaHCO3, water, and
10% citric acid followed by water. The organic phase
was dried over anhydrous MgSO4, and solvent was
removed under reduced pressure. The resulting crude
product was recrystallized from ether and petroleum
ether to obtain 4.68 g of compound I (yield 90.2%).
mp 58–62◦C (lit. 54–62◦C [21]) Anal. calcd for
C26H38N4O7: C 60.21; H 7.38; N 10.80. Found: C
60.24; H 7.35; N 10.79.
−
plexing agents such as OAc−, ClO4 and Cl− in the
form of sodium salts, the formal redox potential Eoꢁ
is 1.126, 1.169, and 1.181 V, respectively. Triply dis-
tilled water was used for preparation of the complexing
agents.
Kinetic Measurements
Mixtures of solution containing requisite amounts of
TETP, sodium acetate (to maintain constant ionic
strength), and water (to keep the total volume con-
stant) were prepared in stoppered boiling tubes. The
mixture was thermally equilibrated in a water bath at
298 K. To the solution in this tube, was added an aliquot
of pre-equilibrated Mn(OAc)3 stock solution to give a
known overall concentration. The progress of the re-
action was monitored for two half-lives by measuring
the absorbance of unreacted Mn(III) at λmax 400 nm.
Plots of log (absorbance) vs. time were linear. The rate
constants kobs calculated from these plots were repro-
ducible within 3% error.
Gly-Gly-Val-Pro (II). Debenzylation of compound I
was achieved by catalytic transfer hydrogenation us-
ing Mg/HCO2H·NH2NH2 [22] to obtain Boc-Gly-Gly-
Val-Pro-OH. This was further deblocked with TFA
(10 mL/g of peptide) by stirring for 40 min. The excess
of TFA was removed under reduced pressure, triturated
with Et2O, and filtered to obtain TFA salt of Gly-Gly-
Val-Pro (yield 100%).
Preparation of Mn(III) Acetate
RESULTS AND DISCUSSION
Mn(OAc)3 was purchased from E. Merk (Mumbai,
India). A solution of 0.02 M Mn(OAc)3 was prepared
by dissolving in 25%(v/v) of acetic acid in water.
To this solution, added 0.5 M solution of sodium ac-
etate, which is not only increases the rate of reaction
but also enhances the solubility of Mn(OAc)3 due to
the formation of acetato complex [Mn(OAc)4]−. Even
though the solution appeared to be stable for more
than two days at [H+] > 5.0 M, it was prepared afresh
daily.
In both the NMR spectra and the HPLC chromatograms
of amino acid analysis, the absence of extraneous peaks
verified the synthesis; and the ratio of relevant peaks
provides the ratios of amino acid residues in TETP, and
the data are depicted in the Table I.
Dependence of Rate
on [Mn(III)] and [TETP]
Kinetic oxidations of these tertramers were performed
by varying concentrations of Mn(III) at constant tem-
perature of 298 K (Table II). Plots of log (absorbance)
vs. time were linear even beyond 75% of the reac-
tion, showing a first-order dependence of the rate on
[Mn(III)]. At constant [Mn(III)]0, [Mn(II)]0 [NaOAc]0,
and temperature, the rate was increased with increase
in [TETP]. Plots of log kobs vs. log [TETP] (Fig. 1) were
linear with slopes of 0.98, 1.01, 1.02, and 0.99 for Gly-
Gly-Ala-Pro, Gly-Gly-Val-Pro, Gly-Gly-Phe-Pro, and
Gly-Gly-Ile-Pro, respectively.
Preliminary Studies
The absorption spectra of Mn(III) solution were
recorded using a Systronics UV-Vis 118 spectropho-
tometer with 3 cm quartz cells. The visible spectrum
of freshly prepared Mn(OAc)3 solution showed λmax
at 440 nm is probably due to undissociated Mn(OAc)3.
But Midgley and Thomas [23] noted that when alkaline
metal acetates were added to Mn(OAc)3 it appears at
400 nm. This is due to the formation of an acetato com-

118
SRINIVASA ET AL.
Table I Amino Acid Composition of Free Peptides
Peptides
Gly
Proa
Ala
Val
Ile
–
Phe
–
GGAP
GGVP
GGIP
2.07(2.00)
2.01(2.00)
2.10(2.00)
1.98(2.00)
1.00
1.00
1.00
1.00
0.98(1.00)
–
–
–
0.98(1.00)
0.97(1.00)
–
GGFP
1.02(1.00)
Theoretical values are in parentheses.
aPro residue was taken as 1.00.
Table II Effect of Varying Reactant Concentration on the Reaction Rate in 25% the Acetic Acid Medium at 298 K
kobs × 105 (s−1
)
[Mn(III)] × 10−3
[TETP] × 10−2
[NaOAc] × 10−1
(mol dm−3
)
(mol dm−3
)
(mol dm−3
)
GGAP
GGVP
GGIP
GGFP
0.7
1.0
1.3
1.6
1.9
2.2
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
12.14
12.01
12.40
12.18
12.21
12.15
9.17
10.87
12.01
13.13
14.66
15.79
16.90
17.85
19.32
19.43
19.46
19.34
19.31
19.48
15.31
17.57
19.43
21.18
22.64
23.98
25.47
26.79
23.26
23.18
23.21
23.16
23.28
23.19
18.20
20.88
23.18
25.19
26.83
29.06
30.22
32.24
28.18
28.22
28.26
28.31
28.19
28.24
22.69
25.67
28.22
30.24
32.34
33.90
35.94
37.14
Dependence of Rate on [Mn(II)], Added
Anions, and Dielectric Constant
The effect on the rate by varying concentrations of
Mn(II), a reduction product, was investigated. Sequen-
tial increase of [Mn(II)] from 0.01 through 0.1 M has
no effect on the rate, indicating that the product is not
involved in a pre-equilibrium with the oxidant. Sim-
ilarly, the effect of anion OAc− was observed as the
rate increased with increase in [NaOAc](0.5–2.5 M).
But increase in the concentration of other anions such
as Cl− (0.01–0.5 M) and ClO4−(0.01–1.0 M) has in-
significant effect on the rate. The effect of dielectric
constant (D) on the rate was studied by varying the
percentage of AcOH composition. The rate decreased
with increase in the AcOH content. A plot of log kobs
vs. 1/D (Fig. 2) was linear with a negative slope in
agreement with the Amis concept for dipole–dipole or
ion–dipole interactions [25].
Figure 1 Effect of [TETP] on the rate at 298 K, [Mn(III)]
= 1.0 × 10−3 mol dm−3, and [NaOAc] = 0.5 mol dm−3
.

Mn(III) OXIDATION OF PEPTIDES
119
found to be linear. The activation energies (Ea) were
calculated from the slopes of plots. From this mean
value, the activation parameters ꢀH=, ꢀS=, ꢀG=,
and the frequency factor (log A) were evaluated and are
presented in Table III. The negative entropies of activa-
tion (ꢀS=) for all TETPs indicate the involvement of a
rigid associated species in the transition state, which is
probably formed due to solvation lowering the entropy
of activation. In addition, positive values for ꢀH= and
ꢀG= indicate that TETPs react with Mn(III) via the
proposed general mechanism.
Test for Free Radicals
Addition of the reaction mixture to aqueous acrylamide
monomer solution initiates polymerization, indicating
the in situ formation of free radical species during the
reaction sequence. Relevant control experiments were
also performed.
Figure 2 Effect of dielectric constant on the rate at the
condition 298 K, [Mn(III)] = 1.0 × 10−3 mol dm−3, [TETP]
= 1.0 × 10−2 mol dm−3, and [NaOAc] = 0.5 mol dm−3
.
Reaction Stoichiometry
and Product Analysis
The mixtures containing TETP (0.001 M), NaOAc
(0.5 M), and excess Mn(III) (0.01 M) were kept
for 24 h at 298 K. The unconsumed Mn(III) was
then determined by the iodometric method. Eight
moles of oxidant was sufficient to oxidize 1 mole of
TETP leading to aldehydes, carbon dioxide, ammonia,
Mn(OAc)2, OAc−, and hydrogen ion. After comple-
tion of the reaction, the reaction mixture was quenched
by pouring it into ice cold water (50 mL). The prod-
ucts were extracted with ether and subjected to col-
umn chromatography on silica gel (60–200 mesh) us-
ing gradient elution (dichloromethane to chloroform).
Aldehydes were analyzed qualitatively by gas chro-
matography. The retention times of formaldehyde,
acetaldehyde, isobutyraldehyde, phenyl acetaldehyde,
and 4-aminobutyaraldehyde are 5.13, 5.92, 27.4, 31.1,
and 32.1 min, respectively, which are identical with
authentic samples. Ammonia and CO2 were detected
by Nessler’s reagent and lime water tests, respectively.
Based on these results the following stoichiometric
equations are suggested (Scheme 1).
Activation Parameters
To determine the activation parameters, the reactions
were carried out at different temperatures (293–313 K).
The Arrhenius plots of log kobs vs. 1/T (Fig. 3) were
It is clearly shown from the previous studies that in
the presence of F− ion, aqueous solutions of Mn(III)
consist of hexa-aquomanganese(III){[Mn(H2O)6]3+},
Mn(III)(aq), hydroxopentaaquomanganese(III) {[Mn
(OH)(H2O)5]2+}, Mn(OH)2+(aq), and MnF2+(aq). And
in sulfuric acid, Mn(III) species present are Mn(III)(aq)
,
Figure 3 Arrhenius plots of log kobs vs. 1/T at the
conditions [Mn(III)] = 1.0 × 10−3 mol dm−3, [TETP] =
1.0 × 10−2 mol dm−3, [NaOAc] = 0.5 mol dm−3, and dif-
ferent temperatures.
+
Mn(OH)2+ , and MnSO4 [11]. But in the present
(aq)
work, Mn(OAc)3 in the acetic acid medium differs
from others with respect to the oxidation of TETPs,

120
SRINIVASA ET AL.
Table III Activation Parameters for the Oxidation of TETP by Mn(III) in 25% (v/v) Acetic Acid Medium
Ea
(kJ mol−1
ꢀH=
(kJ mol−1
ꢀS=
(JK−1 mol−1
ꢀG=
(kJ mol−1
Substrate
)
)
)
)
log A
GGAP
GGAP
GGIP
59.58
54.93
54.14
53.44
56.43
52.45
51.66
50.96
−130.67
−131.63
−141.16
−141.85
95.37
94.68
93.73
93.24
6.52
5.91
5.85
5.81
GGFP
[Mn(III)] = 1.0 × 10−3 mol dm−3, [TETP] = 1.0 × 10−2 mol dm−3, [NaOAc] = 0.5 mol dm−3
.
From the equilibrium step [TETPH+] = k1 [TETP]
which involves the trivalent manganese, [Mn(OAc)3]
or [Mn(OAc)4]− as reaction species.
[H+]
{k1k2k3k4[Mn(OAc)4]−[TETP][H+]}
Rate =
−
Mn(OAc)3 + OAc−
[Mn(OAc)4]
(1)
ꢀ
ꢁ
{k−2k−3[Mn(OAc)2][H+][OAc−]2 + k3k4}
Scheme 2 accounts for the observed experimental
results.
(5)
{k[Mn(OAc)−4 ][TETP][H+]}
Rate =
{k−2k−3[Mn(OAc)2][H+][OAc−]2 + k3k4}
−
d[Mn(OAc)4
]
Since, rate =
= k4[Y]
(2)
dt
(6)
Applying the study state approximation to intermediate
species X and Y, and by subsequent substitution of the
results in Eq. (2), we get
where k = k1k2k3k4.
The observed kinetic results show a first order
on [Mn(OAc)3] and [OAc−], a first-order depen-
dence on [TETP] and an inverse order dependence
on [H+]. Theref−ore, the experimental rate law is rate
= k[Mn(OAc)4 ] [TETP] [H+]/k−2k−3[Mn(OAc)2]
[OAc−]2[H+] + k3k4. Based on these results and lit-
erature studies, a probable mechanism is proposed
for the oxidation of TETP (Scheme 3). In the pro-
posed mechanism, the formation of product, the alde-
hyde, is envisaged due to the reaction of the inter-
mediate TETP free radical with Mn(OAc)−4 . Similar
mechanism has been proposed for the Mn(III) ox-
idation of amino acids in the aqueous acetic acid
medium [26].
Rate =
{k2k3k4[Mn(OAc)4−][TETPH+]}
{k−2k−3[Mn(OAc)2][H+][OAc−]2 + k−2k4 + k3k4}
(3)
Assuming that k−2k4 ꢃ k3k4 in the denominator
then, rate =
{k2k3k4[Mn(OAc)−4 ][TETPH+]}
The rate of oxidation of TETP by Mn(III) was
found to be slower when compared with tripeptides
(4)
{k−2k−3[Mn(OAc)2][H+][OAc−]2 + k3k4}
Scheme 1

Mn(III) OXIDATION OF PEPTIDES
121
Scheme 2
Gly-Ala-Pro, Gly-Val-Pro, Gly-Ile-Pro and Gly-Phe-
Pro, dipeptides, Ala-Pro, Val-Pro, Ile-Pro and Phe-Pro
and free amino acid in the presence of different aque-
ous acid mediums [8–11]. The change in each case is
due to the increased distance between the functional
groups and consequently weaker electrostatic effects.
Hence, the oxidation of the tetrapeptides is expected to
be slower than the amino acids, dipeptides, and tripep-
tides. Further, it was observed that the rate of oxidation
of these TETPs by Mn(III) in the presence of sulfate
ions in the sulfuric acid medium at 298 K is faster than
the oxidation with Mn(OAc)3 in the acetic acid medium
[11]. Based on these and other results discussed ear-
lier, the most probable mechanism is proposed in
Scheme 3.
Spectral Evidence for the Formation
of TETP–Mn(III) Complex
The study of UV-Visible spectra of pure Mn(III),
TETPs (glycyl-glycyl-alanyl-proline, glycyl-glycyl-
valyl-proline, glycyl-glycyl-isoleucyl-proline, and
glycyl-glycyl-phenylalanyl-proline) and mixtures of
Mn(III) and TETP has shown deviations in peak
wavelength (λmax) and absorbance (Abs). The data are
shown in Table IV.

122
SRINIVASA ET AL.
Scheme 3
Table IV UV-Visible Spectral Data of Mn(III), TETP, and Complexes of Mn(III) and TETP
Substrate
λmax (nm)
Abs
Complex
λmax (nm)
Abs
Mn(III)
GGAP
GGVP
GGIP
400.0
215.0
220.0
223.0
222.0
1.205
2.789
2.799
3.000
2.913
Mn(III) + GGAP
Mn(III) + GGVP
Mn(III) + GGIP
Mn(III) + GGFP
236.5
238.0
241.5
237.5
3.338
3.294
3.538
3.134
GGFP

Mn(III) OXIDATION OF PEPTIDES
123
13. Sandberg, L. B.; Leslie, J. G.; Leach, C. T.; Torres, V. L.;
Smith, A. R.; Smith, D. W. Pathol Biol 1985, 33, 266–
274.
14. Yeh, H.; Ornstein-Goldstein, N.; Indik, Z.; Sheppard,
P.; Anderson, N.; Rosenbloom, J. C.; Cicila, G.; Yoon,
K.; Rosenbloom, J. Collagen Related Res 1987, 7, 235–
247.
Conclusion
An apparent correlation was noted between the rate of
oxidation and the hydrophobicity of these sequences,
whereincreasedhydrophobicityresultsintheincreased
rate of oxidation. Further, an aromatic side chain con-
taining amino acid residue is more sensitive to oxida-
tion. The order of rate of oxidation of tetrapeptides was
found to be GGFP > GGIP > GGVP > GGAP which is
in agreement with their hydrophobicity.
15. Sandberg, L. B.; Soskel, N. T.; Leslie, J. B. Engl J Med
1981, 304, 566–579.
16. Gowda, D. C.; Parker, T. M.; Harris, R. D.; Urry, D. W.
In Peptides; Basava, C.; Anantharamaiah, G. M. (Eds.);
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