Antiproliferative properties of chemically modified recombinant IFN-alpha2b.
The antiproliferative activity of aconitylated (AIFN) and succinylated (SIFN) derivatives of recombinant interferon- alpha2b (IFN-alpha2b) was examined. Acylation of IFN-alpha2b was performed by succinic and cis-aconitic anhydrides. Antiproliferative properties of AIFN and SIFN were studied in vitro on the CaOv cell line, highly sensitive to IFN, and on the SW-480 cell line, with low sensitivity to IFN-alpha2b. Acylation of one lysine in the IFN-alpha2b molecule with cis-aconitic or succinic anhydride resulted in a 3-3.5-fold increase of its antiproliferative activity on CaOv cells. The highest antiproliferative activity of acylated IFN-alpha2b on SW-480 cells was observed for both AIFNs and SIFNs with three modified lysine residues. In conclusion, aconitylated and succinylated IFNs may be useful antiproliferative agents for cancer treatment.
Martynov
A V
AV
I.I. Mechnikov Institute of Microbiology and Immunology AMS of Ukraine, Kharkiv 61057, Ukraine. imiamn@mail.ru
Smelyanskaya
M V
MV
D000156:Aconitic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D000215:Acylation; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins; D013387:Succinic Anhydrides / Q000737:chemistry
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013387:Succinic Anhydrides; C064873:aconitic anhydride; C031801:succinic anhydride; D000156:Aconitic Acid