Conformational Analysis of Cysteine -Containing Peptides and Prospects of Their Application to 213 Bi Chelating in Antitumor Therapy
T. V. Gogitidze a , V. P. Demushkin a # , E. V. Zhavoronkova@a , V. V. Kopytov a , and N. S. Marchenkov b
# Phone: +7 (495) 330-6438, e-mail:
vdem@ibch.ru
a
Shemyakin
--
Ovchinnikov
Institute
of
Bioorganic Chemistry
, Russian
Academy
of
Sciences
,
ul
.
Miklukho-Maklaya
, 16/10,
Moscow
, 117997
Russia
b
Russian Scientific Center
Kurchatov
Institute, pl.
Kurchatova
1,
Moscow
, 123182
Russia
Received September 8, 2005; in final form, December, 29, 2005
Abstract: The method of conformational analysis was applied to the spatial structures of peptide analogues of phytochelatins and some fragments of metallothioneins: (Cys-Gly)3, (Cys-Gly)3-Asp, (Cys-Gly)3-Glu, (Cys-βAla)3, (Cys-γGlu)3, and (Cys-Gly-Gly)3. All the possible low-energy conformations of the molecules were revealed and the role of intra- and interresidual interactions in the formation of their spatial structures was determined. A different tendency of the molecules under study for acceptance of conformations favorable for binding bismuth ions was shown. Low-energy structures providing an optimum binding of bismuth ion were shown to be most frequent for (Cys-βAla)3 peptide. Among the analogues of peptide fragments of the metallothioneins, lacking in natural peptides, low-energy pentapeptide CCXXC fragments (where X = Gln, Asn, Phe, Tyr, or Gly) were revealed. In the α-helical conformations of these pentapeptides, the distance between the sulfur atoms corresponds to that in Bi2S3.
Key words: chelators , conformational analysis of peptides, metallothioneins , phytochelatins , radionuclides
Russian Journal of Bioorganic Chemistry 2006, 32 (3):240-247