Antibody-glycosidases Conjugate

As a professional service provider in antibody-drug conjugates (ADCs) design and preparation, Creative Biolabs offers customized antibody-directed enzyme prodrug therapy (ADEPT) development services for global customers.

Glycosidases

Glycosidases, also known as glycoside hydrolases, catalyze the hydrolysis of glycosidic bonds in complex sugars. Glycosidases are found in all of the organisms such as prokaryotes and in higher organisms. Their functions include degradation of biomass, anti-bacterial defense strategies, pathogenesis mechanisms, and normal cellular function. Together with glycosyltransferases, glycosidases make a contribution to the synthesis and breakage of glycosidic bonds. In bacteria (such as E. coli), glycosidases are involved in the regulation of lac operon expression. In higher organisms, glycosidases are found in the Golgi apparatus and endoplasmic reticulum where they are participated in the processing of N-linked glycoproteins, and in the lysosome where they are involved in the degradation of carbohydrate structures.

Fig.1 Glycosidases catalyze the hydrolysis of glycosidic bonds in complex sugars.

MOA of Glycosidases

Glycosidases enzyme can catalyze the hydrolysis of prodrug glycosides yielding the parent drug daunomycin. Daunomycin is a chemotherapy medication used to treat cancer such as acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and Kaposi's sarcoma. It interacts with DNA by intercalation and inhibition of macromolecular biosynthesis. Once antibody-Glycosidases conjugating for ADEPT, Glycosidases catalyze prodrug glycosides to produce daunomycin when the prodrug is administrated into the tumor site, followed accomplish the drug’s cytotoxic effects.

Antibody-glycosidases Conjugate-based ADEPT

The use of antibody-enzyme conjugates directed at tumor-associated antigens to achieve site-specific activation of prodrugs is a conventional and useful strategy for the treatment of cancer. Recently, glycosidases used as the enzyme of ADEPT is under active evaluation. Glycosides are prodrugs of CI-TMI 14 which is a structurally simplified analogue of the highly potent antitumor agent duocarmycin SA 2. It displays very low toxicity when cultured with carcinoma cells of line A549. However, in the ADEPT strategy based on the glycosidases, after addition of the corresponding enzymes and exposure for 24 hr at prodrug concentrations of <0.1 mM, the proliferation of the carcinoma cells was inhibited almost completely with ED_50prodrug/ED_50drug of up to 270 both in the presence and absence of the enzyme.

Fig.2 Mechanism of ADEPT action. (Bagshawe, 2004)

Creative Biolabs provides customers with the best services concerning ADEPT development. Our experienced scientists are dedicated to helping clients develop antibody-glycosidases conjugate in a timely and cost-effective manner. We also provide other services regarding ADEPT development. Please feel free to contact us for more information and a detailed quote.

Reference

1. Bagshawe, K. D.; et al. Antibody-directed enzyme prodrug therapy (ADEPT) for cancer. Expert opinion on biological therapy. 2004, 4(11), 1777-1789.