Download xes, except for the mono-complex which was regu

2nd INTERNATIONAL CONFERENCE ON BIOINORGANIC CHEMISTRY
xes, except for the mono-complex which was regular octahedral, had shorter Ni-O bonds than Ni-N
bonds, and the differences between the Ni-O and
Ni-N distances were more enhanced in the tris-complex than in the bis-complex.
Stepwise formation constants of the glycinato
complexes decreased with the number of glycinato
ions within the complexes. However, the stepwise
formation reactions were more exothermic at a
higher complex than a lower one in the case of
nickel(II) and zinc(II) ions, except for the formation of Zn(gly)3. A more negative value in DII° at
a higher complex is explained in terms of weakened M-OH, bonds in the complex, the water
molecules being more easily replaced by an entering glycinate ion. A large rate constant of formation of a higher complex may also be due to water
molecules which become more labile in the complex by the elongation of the M-0H 2 bond.
The structures of the complexes thus determined
were compared with those of metal complexes
with other amino acids and biologically interesting
ligands and with structures of carboxypeptidase,
carbonic anhydrase and thermolysin in the crystalline state.
REFERENCES
[1] K.
OZUTSUMI,
H.
OHTAKI,
Bull. Chem. Soc. Jpn., 56, 3635
(1983).
[2] K.
OZUTSUMI, T. YAMAGUCHI,
the
H.
OHTAKI, «Abstracts Of
3rd International EXAFS Conference», Stanford,
U.S.A., July 15-20, 1984.
[3] K.
OZUTSUMI,
H.
OHTAKI,
Bull. Chem. Soc. Jpn., 57,
2605 (1984).
[4] K.
[5]
OZUTSUMI,
T. FUJITA, T.
H.
OHTAKI, to be published.
YAMAGUCHI,
H.
OHTAKI,
Bull. Chem. Soc.
Jpn., 52, 3539 (1979).
[6] T.
FUJITA,
H.
OHTAKI,
Bull. Chem. Soc. Jpn., 53, 930
H.
OHTAKI,
Bull. Chem. Soc. Jpn., 55,
(1980).
[7] T.
FunTA,
455
(1982).
[8] T. FunTA, H.
(1983).
OHTAKI,
Rev. Port. Quím., 27 (1985)
Bull. Chem. Soc. Jpn., 56, 3276
6?)
SL6 — MO
H. KOZMWSKI
G. FORMICKA-KOZCOWSKA
Institute of Chemistry
University of Wroclaw
Joliot-Curie 14, 50-383 Wroclaw
Poland
L.D. PETTIT
I. STEEL
School of Chemistry
University of Leeds
LS2 9JT Leeds
England
CAN COPPER(II) IONS ACTIVATE
BIOLOGICALLY SMALL PEPTIDE
MOLECULES?
Many small peptide molecules show very high biological activity, particularly in the central nervous
system where many are active as neurotransmitters
or as opioids. Very frequently these peptides contain proline or tyrosine residues.
Copper is a biologically essential element which is
distributed unevenly throughout the body, with
relatively high concentrations being found in the
brain. In some cases traces of copper have been
shown to increase the activity of biologically active small molecules (e.g. aspirin and cimetidine
[ 1 , 2]).
The biologically active form of oligopeptides is
usually of an organized structure containing e.g.
one or more beta-turns. The proline residue encourages the formation of such beta-turns [3] and
is unique among biological peptide residues in
that it contains a secondary nitrogen atom which,
when part of a peptide chain, is not bonded to an
ionizable proton and hence cannot coordinate to
copper(II). It therefore acts as a «break-point» to
metal coordination since it allows the two ends of
the chain to coordinate independently. Since a
proline residue also encourages a beta-turn, the
effect is to bring the two chains close together
where they can be bridged by a copper ion [4-6].
Hence the copper can be regarded as locking the
19
SESSION LECTURES
peptide into the biologically active conformation,
so promoting its biological activity ]7].
The specificity of a proline residue as a «break-point» is also seen in its influence on the binding
capability of other amino acid residues present in
the peptide sequence, such as tyrosine [8] and lysine [9] residues. The involvement of ionized tyrosine phenolate oxygen in metal ion binding may
be an important factor in peptides which display
opioid activity such as casomorphin [10].
Copper(II) ions can also affect adversely the biological activity of peptides by binding (and so blocking) their active residues or can promote the activity by «bridging» the peptide to its receptors.
This latter situation is most likely in the case of
metal-TRF system [11,12].
KENNETH D. KARLIN
YILMA GULTNEH
RICHARD W. CRUSE
JON C. HAYES
JON ZUBIETA
Department of Chemistry
State University of New York (SUNY) at Albany
Albany
New York, 12222
U.S.A.
DIOXYGEN BINDING AND ACTIVATION
IN DINUCLEAR COPPER COMPLEX
SYSTEMS
REFERENCES
L.W. OBERLEY, V. KISHORE, S.W.C.
T.D. OBERLEY, A. PEZESHK, Inorg. Chim.
Acta, 79, 45 (1983).
[2] F.T. GREENAWAY, L.M. BROWN, J.C. DABROWIAK, M.R.
THOMPSON, V.M. DAY, J. Am. Chem. Soc., 102, 7782
(1980).
[3] R.Y. CHOU, G.D. FASMAN, J. Mol. Biol., 115, 135
(1977); M. LISOWSKI, LZ. SIEMION, K. SOBCZYK, Int. J.
Pept. Protein Res., 21, 301 (1983) and references therein.
[1] J.R.J.
SL7 — MO
SORENSON,
LEUTHAUSER,
[4]
G. FORMICKA-KOZrAWSKA,
MION,
K.
E.
SOBCZYK,
H.
KOZrnwsKI, 1.Z. SIE-
NAWROCKA,
J. Inorg. Biochem.,
15, 201 (1981).
[5] M. BATAILLE, G.
FORMICKA-KOZLOWSKA, H. KosroL.D. PETTIT, 1 . STEEL, J. Chem. Soc., Chem. Commun., 231 (1984).
[6] L.D. PETTIT, 1 . STEEL, G. FORMICKA-KOZrOWSKA, T.
wSKI,
TATAROWSKI,
M.
BATAILLE,
J. Chem. Soc., Dalton
Trans., in press.
[7] L.D.
PETTIT,
G.
FORMICKA-KOZCOWSKA,
Neuroscience
Letters, 50, 53 (1984).
[8] H.
B.
KOZPDWSKI, M. BEZER,
HECQUET,
[9] M.
T.
BATAILLE,
L.D.
TATAROWSKI,
[10] G.
L.D.
PETTIT,
M.
BATAILLE,
J. Inorg. Biochem., 18, 231 (1983).
PETTIT,
I.
STEEL,
H.
KOZLOWSKI,
J. Inorg. Biochem., in press.
FORMICKA-KOZIDWSKA,
L.D.
PETTIT, 1. STEEL,
B.
K. NEUBERT, P. REKOWSKI, G. KUPRYSZEWSKI, J. Inorg. Biochem., 22, 155 (1984).
[11] G. FORMICKA-KOZLOWSKA, L.D. PETTIT, M. BEZER,
J. Inorg. Biochem., 18, 335 (1983).
[12] T. TONOUE, S. MINAGAWA, N. KATO, K. OHKI, Pharmacol. Biochem. Behav., 10, 201 (1979).
HARTRODT,
Studies of the reactivity of dioxygen with model
mono- and dinuclear copper(I) centers are of interest because of their relevance to the copper proteins such as hemocyanin, a dioxygen carrier, and
tyrosinase and dopamine beta-hydroxylase which
are monooxygenases involved in oxygen activation
[1]. Such model studies may also help in the development of synthetic reagents or catalysts for the
oxidation of organic substrates. Here, we will
summarize our latest findings in several systems
involving Cu(I)-dioxygen interactions or reactivity.
The first deals with a monooxygenase model
system where the reaction of dioxygen with a
dinuclear Cu(I) complex II results in the oxygenation of the ligand and concomitant formation of
the phenoxo- and hydroxo- bridged dinuclear
complex III. Studies using isotopically labelled
dioxygen and the observed stoichiometry of reaction (Cu:0 2 = 2:1) demonstrate that this reaction
is directly analogous to that shown by the copper
mono-oxygenase enzymes [2].
Recent insights into the mechanism of this reaction will be presented. The reaction of a dinuclear
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Y
rN
0 N
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II
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Rev. Port. Quim., 27 (1985)