Synthesis of Reactive Polymers for Acrolein Capture Using AGET ATRP.
Acrolein is a toxic metabolite of the anticancer agent cyclophosphamide (CP). Current strategies to mitigate acrolein toxicity are insufficient, and in this brief article, we report the synthesis of well-defined low molecular weight block copolymers using activators generated by electron transfer atom transfer radical polymerization (AGET ATRP) capable of reacting with the cytotoxic small molecule acrolein. Acrolein reactivity was introduced into the block copolymers via incorporation of either (a) aminooxy or (b) sulfhydryl groups. The cytoprotective effect of the polymers was compared to sodium 2-sulfanylethanesulfonate (mesna) the current gold standard for protection from CP urotoxicity, and we found that the polymers bearing sulfhydryl moieties demonstrated superior cytoprotective activity.
Laboratory for Biomolecular Medicine, Allegheny Health Network Research Institute, Allegheny General Hospital Pittsburgh, Pennsylvania 15212, United States.
Laura T
LT
Beringer
Laboratory for Biomolecular Medicine, Allegheny Health Network Research Institute, Allegheny General Hospital Pittsburgh, Pennsylvania 15212, United States.
Shaohua
S
Li
Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, AHN , Pittsburgh, Pennsylvania 15224, United States.
Gary
G
Gilmore
Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, AHN , Pittsburgh, Pennsylvania 15224, United States.
John
J
Lister
Laboratory for Biomolecular Medicine, Allegheny Health Network Research Institute, Allegheny General Hospital Pittsburgh, Pennsylvania 15212, United States.
Saadyah
S
Averick
D000171:Acrolein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003520:Cyclophosphamide / Q000378:metabolism; D057809:HEK293 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015080:Mesna / Q000494:pharmacology; D058105:Polymerization; D020011:Protective Agents / Q000138:chemical synthesis*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis
D020011:Protective Agents; D013438:Sulfhydryl Compounds; D000171:Acrolein; D003520:Cyclophosphamide; D015080:Mesna
AGET ATRP; acrolein capture; cyclophosphamide Thiol-ene RDRP