Document Type

Poster

Publication Date

4-25-2024

Disciplines

Biochemistry | Chemistry

Advisor

Ed McIntee

Abstract

Low molecular weight protein tyrosine phosphatase (LMW-PTP) is an enzyme and a known signal pathway for growth factors and cellular transformation in eukaryotic cells. Our research aims to synthesize 12 new potential inhibitors of LMW-PTP and analyze their inhibitory activity and binding affinity. The inhibition of both isoforms of LMW-PTP has been the primary focus of research due to their potential role in breast, colon, and other cancers as well as type II diabetes. One known inhibitor, pyridoxal 5’- phosphate (PLP), is essential for various enzymatic reactions within the body, such as the synthesis of neurotransmitters, and is therefore impractical for inhibitory needs. Our current research involves performing computer modeling and the experimental synthesis of 3-(2,6-disubstituted 5-pyrimidyl) propionic acids as potential inhibitors of LMW-PTP. Amidine derivatives are condensed with molecules containing an aldehyde or ketone. These molecules undergo intramolecular cyclization and aromatization to form compounds A-F. The resulting 6 aromatic compounds are subjected to one reaction pathway where the ethyl ester is cleaved. The aromatic compounds can also be subjected to a second reaction pathway where the chloro esters are cyclized and alkaline hydrolysis of the lactams yields the potential inhibitors. All compounds were analyzed using IR, 13CNMR, 1HNMR, and COSY spectra. All compounds were docked into isoform A and isoform B of LMW-PTP to predict a binding affinity. The potential inhibitors were designed in the Spartan program in VMware Horizon Client and docked using SwissDock.

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