ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P124. The Impact the α-COOH Group on the Binding Abilities of the
Simple Tetrapeptides with βAsp-His-Gly-His Sequence
A. Matera-Witkiewicz a , J. Brasuń a , M. Cebrat b , J. Świątek-Kozłowska a
a) Department of Inorganic Chemistry, Wroclaw Medical University, Szewska 38, 50-139 Wroclaw, Poland;
b)Faculty of Chemistry, Wroclaw University, F. Joliot-Curie 14, 50-383 Wroclaw, Poland;
e-mail:amatera@chnorg.am.wroc.pl
Histidine has significant role in many interactions of peptides and proteins with metal ions. The multi-His
sequence is basic for Cu 2+ binding motifs in amyloid precursor protein (APP) [1] or secreted protein, acidic and
rich in cysteine (SPARC) [2, 3]. The recent studies show that prions from many species in their function may
involve copper binding motif with multi-His region [3].
Moreover, Armstrong et al. have shown that in the blood stream a low molecular fractions of Cu 2+ complexes
have been detected with the fraction bound to macromolecular ligand such as serum albumin with Asp-Ala-His-
system [4].
The investigations for the simple tetrapeptides including two His residues in the peptide sequence and β-aspartic
acid or β-alanine are presented. The analysis of the potentiometric as well as spectroscopic results shows that the
presence of the β–aspartic acid in the first position in the peptide chain makes the imidazole rings binding (and
formation of the CuHL and CuL complexes) much more difficult (Fig.1). Furthermore, the binding of the first
amide nitrogen occurs at lower pH in comparison to its α-analogue.
%Cu 2+
100
80
60
40
20
CuHL
CuH 2 L
Cu 2+
CuL
CuH -1 L
0
2 4 6 8 10
pH
CuH -2 L
CuH -3 L
Figure 1. Distribution diagram of complexed species formed as a function of pH in
the β-DHGH -Cu 2+ (solid line) and DHGH-Cu 2+ data from [5] (dashed line) systems
References:
[1] M. Łuczkowski, K. Wiśniewska, L. Łankiewicz, H. Kozłowski, J. Chem. Soc. Dalton Trans., , 2266 (2002)
[2] H. Kozłowski, D.R Brown, G. Valensin, Royal Society of Chemistry in ”Metallochemistry of
Neurodegeneration; biological, chemical and genetic aspects”, (2006)
[3] E. Gagelli, H. Kozłowski, D. Valensin, G. Valensin, Chem. Rev., 106, 1995, (2006),
[4] P.W. Jones, D.M. Taylor, D.R. Williams, J. Inorg. Biochem., 81, 1, (2000),
[5] A.Matera-Witkiewicz, JBrasuń, J.Świątek-Kozłowska, A.Pratesi, M.Ginnaneschi, L.Messori, data unpulished
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