Drug intelligence / Profile preview

deglycosylated ricin A-chain

Development stage
Discontinued
Lead developer
UT Southwestern Medical Center
Modality
Recombinant Proteins and Enzymes
Administration
Intravenous
01

Overview

Deglycosylated ricin A-chain (dgA) is a modified form of the A-chain of ricin, a potent Type II ribosome-inactivating protein (RIP) derived from the castor bean (*Ricinus communis*). The native ricin A-chain is a glycoprotein; however, its carbohydrate residues (mannose and fucose) lead to rapid clearance from the circulation by the liver's reticuloendothelial system. Deglycosylation is performed chemically or enzymatically to remove these sugars, thereby extending the protein's serum half-life and reducing non-specific hepatic toxicity. As a catalytic toxin, dgA functions as an RNA N-glycosidase that specifically and irreversibly depurinates the A4324 residue in the sarcin/ricin loop of the 28S ribosomal RNA. This modification prevents the binding of elongation factors (EF-1 and EF-2) to the ribosome, leading to the total cessation of protein synthesis and subsequent cell death via apoptosis. dgA is primarily utilized as the cytotoxic payload in immunotoxins, where it is chemically linked to monoclonal antibodies (such as anti-CD7 or anti-CD22) to target specific malignancies, particularly hematologic cancers like T-cell leukemia and B-cell lymphomas.

Other names
deglycosylated ricin toxin A-chaindeglycosylated RTA
02

Targets

SRL (28S rRNA sarcin-ricin loop)

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