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

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P33. Effect of Sodium Cations on the Conformational Preferences
of Peptides Bridged by PEG Linkers
M. Cydzik, P. Pasikowski, A. Kluczyk, M. Biernat, M. Lisowski Z. Szewczuk
Faculty of Chemistry, University of Wrolaw, F. Joliot-Ciurie 14, Wroclaw, Poland
Ubiquitin is a small protein (8 kDa) that occurs in all eukaryotic cells. Its main known function is to mark other
proteins for proteolytic degradation. According to our previous results, decapeptide fragment of the ubiquitn
with LEDGRTLSDY sequence exhibits a very strong immunosuppressive activity, comparable to that of
cyclosporin [1]. Recently, we revealed that proper dimerization of some other immunosuppressory peptides
enhanced their biological activity [2,3]. It has been proposed that the dimerized peptides enhance simultaneous
interaction with two hypothetic receptors located in close proximity on T-cells.
We synthesized a series of new analogs of the immunosuppressive decapeptide fragment of ubiquitin. We used
set of polyethylene glycol (PEG) linkers to connect monomeric analogs in various way. The PEG bridge serves
not only as a dimerizer but also as a group which improves the solubility in water.
Three different methods of dimerization of the ubiquitin immunosuppressory fragment. Bold line represents PEG linkers.
The interaction of sodium ions with PEG in the designed dimers results in the creation of noncovalent adducts,
that may affect overall conformation of the dimeric peptides in solution. We performed conformational analysis
by CD spectroscopy to evaluate effect of sodium ions on the conformation of the analogs pegylated in different
ways.
References:
[1] Z. Szewczuk, P. Stefanowicz, A. Wilczyński, A. Staszewska, I.Z. Siemion, M. Zimecki, Z. Wieczorek,
Biopolymers, 74, 352 (2004).
[2] Z. Szewczuk, M. Biernat, M. Dyba, M. Zimecki, Peptides, 25, 207 (2004).
[3] M. Biernat, P. Stefanowicz, M. Zimecki, Z. Szewczuk, Bioconjugate Chem., 17, 1116 (2006).
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