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NOVEL PHOTOCLEAVABLE PROTEIN CROSSLINKING REAGENTS AND THEIR USE IN THE PREPARATION OF ANTIBODY‐TOXIN CONJUGATES
Author(s) -
Senter Peter D.,
Tansey Marilyn J.,
Lambert John M.,
Blattler Walter A.
Publication year - 1985
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1985.tb08936.x
Subject(s) - chemistry , conjugate , reagent , toxin , antibody , diphtheria toxin , covalent bond , combinatorial chemistry , biochemistry , organic chemistry , biology , immunology , mathematical analysis , mathematics
— Two photolabile heterobifunctional protein crosslinking reagents have been synthesized and used for the conjugation of a protein toxin to an antibody. o‐Nitrobenzyl alcohol derivatives containing protected sulfhydryl groups were converted to o‐nitrobenzyloxycarbonyl chlorides and covalently attached to pokeweed antiviral protein (PAP‐S) obtained from the seeds of Phytolacca americana. The sulfhydryl groups were deprotected and the modified toxins were reacted with J5 antibody (specific for the common acute lymphoblastic leukemia antigen, CALLA) that had been functionalized with maleimido groups. Antibody‐toxin conjugates were formed predominantly in the ratio of 1:1, and were purified from unconjugated antibody and PAP‐S. Irradiation of the conjugates with light having a peak intensity at 365 nm effected photolytic fragmentation, and PAP‐S was released in fully active form. The methods described here may prove useful for the release of drugs or toxins at sites accessible to light.