Photoactivation of toxin conjugates.
A novel photocleavable protein cross-linking reagent has been used for conjugation of the ribosome-inactivating protein pokeweed antiviral protein from seeds of Phytolacca americana (PAP-S), with either the monoclonal antibody 5E9 directed against the human transferrin-receptor or the B-chain of ricin that binds to cell-surface oligosaccharides bearing terminal D-galactose residues. When irradiated with near-UV light (350 nm), the linker of these conjugates undergoes photolytic degradation, resulting in the release of native toxin that is fully functional. The cytotoxicities of these 5E9-PAP-S and ricin B-chain-PAP-S conjugates for HeLa cells could be enhanced by irradiating the cells with light after they had internalized the conjugates.
Goldmacher
V S
VS
ImmunoGen, Inc., Cambridge, Massachusetts 02139.
Senter
P D
PD
Lambert
J M
JM
Blättler
W A
WA
D000911:Antibodies, Monoclonal / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry / Q000633:toxicity*; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000737:chemistry / Q000633:toxicity*; D011990:Receptors, Transferrin / Q000276:immunology; D054789:Ribosome Inactivating Proteins, Type 1; D012270:Ribosomes / Q000187:drug effects; D012276:Ricin / Q000737:chemistry; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D000922:Immunotoxins; D010940:Plant Proteins; D011990:Receptors, Transferrin; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein