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:
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