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Modified bleomycin disaccharides exhibiting improved tumor cell targeting.

Madathil MM, Bhattacharya C, Yu Z, Paul R, Rishel MJ, Hecht SM - Biochemistry (2014)

Bottom Line: In earlier studies, we have demonstrated that the tumor cell selectivity resides in the mannose carbamoyl moiety of the BLM saccharide and that both the BLM disaccharide and monosaccharide containing the carbamoyl moiety were capable of the delivery/uptake of a conjugated cyanine dye into cultured cancer cell lines.A library of seven disaccharide-Cy5** dye conjugates was prepared that are structural analogues of the BLM disaccharide.These differed from the natural BLM disaccharide in the position, orientation, and substitution of the carbamoyl group.

View Article: PubMed Central - PubMed

Affiliation: Center for Bioenergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University , Tempe, Arizona 85287, United States.

ABSTRACT
The bleomycins (BLMs) are a family of antitumor antibiotics used clinically for anticancer chemotherapy. Their antitumor selectivity derives at least in part from their ability to target tumor cells, a property that resides in the carbohydrate moiety of the antitumor agent. In earlier studies, we have demonstrated that the tumor cell selectivity resides in the mannose carbamoyl moiety of the BLM saccharide and that both the BLM disaccharide and monosaccharide containing the carbamoyl moiety were capable of the delivery/uptake of a conjugated cyanine dye into cultured cancer cell lines. Presently, the nature of the participation of the carbamoyl moiety has been explored further to provide compounds of utility for defining the nature of the mechanism of tumor cell recognition and uptake by BLM saccharides and in the hope that more efficient compounds could be identified. A library of seven disaccharide-Cy5** dye conjugates was prepared that are structural analogues of the BLM disaccharide. These differed from the natural BLM disaccharide in the position, orientation, and substitution of the carbamoyl group. Studies of these compounds in four matched sets of tumor and normal cell lines revealed a few that were both tumor cell selective and internalized 2-4-fold more efficiently than the natural BLM disaccharide.

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General Strategyfor the Synthesis of Disaccharide–Dye Conjugates
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sch1: General Strategyfor the Synthesis of Disaccharide–Dye Conjugates


Modified bleomycin disaccharides exhibiting improved tumor cell targeting.

Madathil MM, Bhattacharya C, Yu Z, Paul R, Rishel MJ, Hecht SM - Biochemistry (2014)

General Strategyfor the Synthesis of Disaccharide–Dye Conjugates
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222530&req=5

sch1: General Strategyfor the Synthesis of Disaccharide–Dye Conjugates
Bottom Line: In earlier studies, we have demonstrated that the tumor cell selectivity resides in the mannose carbamoyl moiety of the BLM saccharide and that both the BLM disaccharide and monosaccharide containing the carbamoyl moiety were capable of the delivery/uptake of a conjugated cyanine dye into cultured cancer cell lines.A library of seven disaccharide-Cy5** dye conjugates was prepared that are structural analogues of the BLM disaccharide.These differed from the natural BLM disaccharide in the position, orientation, and substitution of the carbamoyl group.

View Article: PubMed Central - PubMed

Affiliation: Center for Bioenergetics, Biodesign Institute, and Department of Chemistry and Biochemistry, Arizona State University , Tempe, Arizona 85287, United States.

ABSTRACT
The bleomycins (BLMs) are a family of antitumor antibiotics used clinically for anticancer chemotherapy. Their antitumor selectivity derives at least in part from their ability to target tumor cells, a property that resides in the carbohydrate moiety of the antitumor agent. In earlier studies, we have demonstrated that the tumor cell selectivity resides in the mannose carbamoyl moiety of the BLM saccharide and that both the BLM disaccharide and monosaccharide containing the carbamoyl moiety were capable of the delivery/uptake of a conjugated cyanine dye into cultured cancer cell lines. Presently, the nature of the participation of the carbamoyl moiety has been explored further to provide compounds of utility for defining the nature of the mechanism of tumor cell recognition and uptake by BLM saccharides and in the hope that more efficient compounds could be identified. A library of seven disaccharide-Cy5** dye conjugates was prepared that are structural analogues of the BLM disaccharide. These differed from the natural BLM disaccharide in the position, orientation, and substitution of the carbamoyl group. Studies of these compounds in four matched sets of tumor and normal cell lines revealed a few that were both tumor cell selective and internalized 2-4-fold more efficiently than the natural BLM disaccharide.

Show MeSH
Related in: MedlinePlus