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Slideshow

Chemical approaches to challenging drug delivery problems: From gasotransmitters to enrichment-triggered release

Prof. Binghe Wang
Prof. Binghe Wang
Department of Chemistry
Georgia State University
Chemistry Building, Room 400
Organic Seminar

Abstract: Prodrug approaches are often used to solve drug delivery problems. In doing so, the chemistry needed to bioreversibly derivatize the drug molecule is the key. Along this line, bioreversible derivatization of gasotransmitters such as nitric oxide, hydrogen sulfide and carbon monoxide are especially challenging. Furthermore, the chemistry used to prepare antibody-drug conjugates also has much room for improvement. This presentation will discuss some unique chemistry developed for the preparation of prodrugs of carbon monoxide and hydrogen sulfide as well as a new approach to prodrug activation through enrichment.

Keyword: gasotransmitter, antibody-drug conjugates, carbon monoxide, hydrogen sulfide

Key Reference:

  1. Zheng, Y.; Ji, X.; Yu, B.; Ji, K.; Gallo, D.; Csizmadia, E. Zhu, M.; De La Cruz, L.K.; Choudhary, M.R.; Chittavong, V.; Pan, Z.; Yuan, Z.; Otterbein, L.; Wang, B. “Enrichment-triggered Prodrug Activation Demonstrated through Mitochondria-targeted Delivery of Doxorubicin and Carbon Monoxide” Nature Chem. 2018, 10, 787-794.
  2. Ji. X.; Wang, B. “Strategies towards Organic Carbon Monoxide Prodrugs” Acc. Chem. Res. 2018, 51, 1377-85.
  3. Correa-Costa, M.; Gallo, D.; Csizmadia, E.; JI, X.; Lieberum, J.-L.; Hauser, C.J.; Wang, B.; Camara, N.O.S.; Robson, S.C.; Otterbein, L. E. “Carbon monoxide protects the kidney through the central circadian clock and CD39Proc. Natl. Acad. Sci. 2018, 115, E2302-E2310
  4. Yu, B.; Zheng, Y.; Yuan, Z.; Li, S.; Zhu, H.; De La Cruz, L. K.; Zhang, J.; Ji, K.; Wang, S.; Wang, B. “Toward Direct Protein S-Persulfidation: A Prodrug Approach that Directly Delivers Hydrogen Persulfide” J. Am. Chem. Soc. 2018, 140, 30-33.
  5. Zheng, Y.; Yu, B.; De La Cruz, L.K.; Chaudhary, M.; Anifowose, A. “Toward Hydrogen Sulfide–Based Therapeutics: Critical Drug Delivery and Developability Issues” Med. Res. Rev., 2018, 38, 57-100

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