Synthesis of Boron-Containing Structural Building Blocks For Use in Potential Protease Enzyme Inhibitors

Document Type

Poster

Campus where you would like to present

Ellensburg

Event Website

https://digitalcommons.cwu.edu/source

Start Date

18-5-2020

Abstract

1,3-Azaborines have good potential to function as dual-mode, both associative and competitive, inhibitors of protease enzymes, which are involved in the development of several disease states, including the Human Immunodeficiency Virus (HIV) infection/acquired immunodeficiency syndrome (AIDS), malaria, Alzheimer’s, and some forms of cancer. In our syntheses boron-modified amino acids (including boronated phenylalanine and isoleucine) are being developed as chemical precursors, which are then incorporated into larger boronates in order to obtain the biologically relevant 1,3-azaborines. The target 1,3-azaborines were designed to complement the structure of the enzyme’s chiral active site. In our synthetic schemes pinacol and (1R,2R)-1,2-dicyclohexyl-1,2-ethanediol are both used as protecting groups, while (1R,2R)-1,2-dicyclohexyl-1,2-ethanediol is also used as a chiral director. The target boronates have the potential for greater affinity towards protease enzymes, dual-mode of action, increased bioavailability, and fewer adverse side effects. Many studies have shown that boron-modified inhibitors have a higher inhibitory affinity for protease enzymes than the corresponding non-boron analogs. The non-boron analogs are experiencing high resistance rates, low bioavailability, and patient noncompliance due to adverse side effects. As a result, there is a higher demand for the development of new compounds to combat these diseases.

Faculty Mentor(s)

Levente Fabry

Department/Program

Chemistry

Additional Mentoring Department

https://cwu.studentopportunitycenter.com/2020/04/synthesis-of-boron-containing-structural-building-blocks-for-use-in-potential-protease-enzyme-inhibitors/

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May 18th, 12:00 PM

Synthesis of Boron-Containing Structural Building Blocks For Use in Potential Protease Enzyme Inhibitors

Ellensburg

1,3-Azaborines have good potential to function as dual-mode, both associative and competitive, inhibitors of protease enzymes, which are involved in the development of several disease states, including the Human Immunodeficiency Virus (HIV) infection/acquired immunodeficiency syndrome (AIDS), malaria, Alzheimer’s, and some forms of cancer. In our syntheses boron-modified amino acids (including boronated phenylalanine and isoleucine) are being developed as chemical precursors, which are then incorporated into larger boronates in order to obtain the biologically relevant 1,3-azaborines. The target 1,3-azaborines were designed to complement the structure of the enzyme’s chiral active site. In our synthetic schemes pinacol and (1R,2R)-1,2-dicyclohexyl-1,2-ethanediol are both used as protecting groups, while (1R,2R)-1,2-dicyclohexyl-1,2-ethanediol is also used as a chiral director. The target boronates have the potential for greater affinity towards protease enzymes, dual-mode of action, increased bioavailability, and fewer adverse side effects. Many studies have shown that boron-modified inhibitors have a higher inhibitory affinity for protease enzymes than the corresponding non-boron analogs. The non-boron analogs are experiencing high resistance rates, low bioavailability, and patient noncompliance due to adverse side effects. As a result, there is a higher demand for the development of new compounds to combat these diseases.

https://digitalcommons.cwu.edu/source/2020/COTS/40