Synthesis and Structure–Function Study of Artificial Nucleases on the Basis of Hemin Conjugates with Peptide Fragments of Cell Differentiation Factor HLDF

G. A. Zheltukhina a , # T. N. Lobanova a , V. E. Nebolsin a , M. O. Gallyamov b , S. M. Dranitsyna c , and I. A. Kostanyan c

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a Lomonosov State Academy of Fine Chemical Technology, pr. Vernadskogo 86, Moscow, 119571, Russia

b Faculty of Physics, Moscow State University , Vorob'evy gory, Moscow , 119899 Russia

c Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences , ul. Miklukho-Maklaya 16/10, Moscow , 117997 Russia

Received July 22, 2005; in final form, September 22, 2005

Abstract: A series of octa–hexapeptide fragments of HLDF and their conjugates with hemin were obtained by solid phase peptide synthesis. A relationship between the structure and the nuclease activity of the compounds was established. The effect of various factors (medium pH, the presence of metal ions, complexons, reducers, and buffer composition) on DNA destruction with hemin peptides was studied. Preliminary information confirming an oxidative mechanism of this process was obtained. The cleavage of plasmid DNA under the action of hemin peptides was studied by the methods of electron microscopy, gel electrophoresis, and atomic force microscopy.

Key words: atomic force microscopy, differentiation factor, DNA, hemin peptides, HLDF , nuclease activity, solid phase synthesis

Russian Journal of Bioorganic Chemistry 2006, 32 (2):179-190