Immunotoxins containing A‐chain of mistletoe lectin I are more active than immunotoxins with ricin A‐chain

FEBS Letters

Agapov, Igor I.³  Kirpichnikov, Michail P.²  Shamshiev, Abdijapar T.³  Pohl, Peter¹  Temyakov, Dmitryi E.³  Tonevitsky, Alexander G.³ 

[1] Department of Medical Physics and Biophysics, Martin Luther University, Str. OdF 6, 06097 Halle, Germany;Institute of Molecular Biology, Russian Academy of Science, Vavilov st., 32, 117984 Moscow, Russian Federation;State Scientific Center for Genetics and Selection of Microorganisms, 1st Dorozhny pr. 1, Moscow 113545, Russian Federation

关键词: Immunotoxin;    Ricin;    Mistletoe lectin I;    monAB;    monoclonal antibody;    IT;    immunotoxin;    MLI;    mistletoe lectin I;    MLIA;    mistletoe lectin I A-chain;    RTB;    ricin B-chain;    RTA;    ricin A-chain;    DTT;    dithiotreitol;    PBS;    phosphatebuffered saline;    BSA;    bovine serum albumin;    DMPC;    dimyristoylphosphatidylcholine;    ANS;    1-anilinenaphthalene-8-sulfonate;    IC50;    toxin concentration causing 50% inhibition of [3H]thymidine incorporation into cells;   

DOI  :  10.1016/0014-5793(96)00803-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Conjugates of anti-CD25 monoclonal antibodies against cell surface IL-2 receptor with MLIA and RTA were prepared and investigated. Both of the immunotoxins had high specific cytotoxic activity on target cells. The IC₅₀ value of the anti-CD25/MLIA immunotoxin was 15-fold greater than that of the anti-CD25/RTA. Previous studies of the anti-CD5 immunotoxins with MLIA and RTA showed that the anti-CD5/MLIA IT was 80-fold more active than anti-CD5/RTA IT [Tonevitsky et al. (1991) Int. J. Immunopharmacol. 13, 1037–1041]. The surface hydrophobicity of the MLI A-chain was 4-fold higher than that of the ricin A-chain as estimated by binding with ANS. In model experiments with small unilamellar DMPC liposomes, MLIA but not RTA increased the turbidity of liposome suspensions at pH 4.5. Our results indicate that the greater cytotoxic activity of the MLI A-chain immunotoxin probably provided a higher surface hydrophobicity of the protein and the ability to interact with phospholipid membranes.

【 授权许可】

Unknown