Russian Journal of Bioorganic Chemistry, Vol. 29, No. 1, 2003, đ . 26

An Artificial Protein with the Biological Activity of the Differentiation Factor for the HL-60 Cell Line of Human Promyelocyte Leukemia

R. V. Chertkova, 1 I. A. Kostanyan, M. V. Astapova, E. A. Surina, D. A. Dolgikh, and M. P. Kirpichnikov

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

Abstract: The ABB-df artificial protein was prepared by inserting the TGENHR biologically active peptide corresponding to the 41–46 sequence of the differentiation factor for the HL-60 cell line of the human promyelocyte leukemia into the N-terminus of the polypeptide chain of albebetin, an artificial protein with the preset structure. The ABB-df protein was found to induce the differentiation of HL-60 cells and to inhibit their proliferation; its efficiency was almost the same as that of the starting peptide. According to CD spectroscopy, the inclusion of the peptide fragment into albebetin exerts virtually no effect on the regular secondary structure of albebetin.

Key words: albebetin, artificial proteins, HLDF-6 peptide, HLDF differentiation factor, HL-60 cell line

Russian Journal of Bioorganic Chemistry, Vol. 29, No. 3, 2003, đ . 231

Artificial Proteins with Antiviral Properties of -Interferons

R. V. Chertkova*, 1 Z. Kh. Abdullaev*, 2 D. A. Dolgikh*, V. P. Zav’yalov**, and M. P. Kirpichnikov*

*Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, GSP Moscow, 117997 Russia, **Chair of Biomedicinal Biotechnologies, Russian University of Peoples Friendship , ul. Miklukho-Maklaya 6, GSP Moscow , 117198 Russia

Abstract: Consensus 30–36 sequence LKDRHDF of human -interferons is inserted into the C- and N-terminal sequences of the artificial protein albeferon using genetic engineering methods in order to obtain artificial proteins with antiviral activity. Albeferon, obtained by Dolgikh et al. (Protein Eng., 1996, vol. 9, pp. 195–201), already contains the IFN- 130–137 fragment and possesses antiproliferative activity comparable with that of IFN-2. According to CD spectroscopy, both proteins have regular secondary structures similar to that of the precursor protein. They exhibit antiviral activities, and the activity of one of them is comparable with that of IFN-2. At the same time, their cytotoxic properties are displayed only at relatively high concentrations, which substantially exceed the minimal antiviral concentrations.

Key words: albebetin, albeferon, 2 -interferon, antiviral activity, artificial proteins