Date of Award
2017
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Graduate Group
Chemistry
First Advisor
Jeffrey D. Winkler
Abstract
The development of small molecule allosteric inhibitors of carbon monoxide (CO) binding to hemoglobin (Hb) is important for the treatment of CO poisoning. We have found that the synthetic peptide IRL 2500 leads to inhibition of CO binding, but with concomitant hemolytic activity. We describe herein the design, synthesis and biological evaluation of analogs of IRL 2500 that inhibit CO binding without hemolysis. The most potent compounds that we have prepared to date contain heteroaromatic biaryls in place of the biphenyl moiety of IRL 2500. These compounds show improved solubility and reduced hemolytic activity. We also describe the synthesis of conformationally constrained analogs of IRL 2500 based on a piperazine-derived scaffold.
Recommended Citation
Goldstein, Sara Rebecca, "The Design And Synthesis Of Allosteric Effectors Of Carbon Monoxide Binding To Hemoglobin" (2017). Publicly Accessible Penn Dissertations. 2313.
https://repository.upenn.edu/edissertations/2313