Publication Title

Journal of Undergraduate Chemistry Research

Synthesis of a Novel RAS Farnesyl Protein Transferase Inhibitor

Authors

Mark F. Mechelke, St. Cloud State UniversityFollow
Anna Mikolchak, St. Cloud State UniversityFollow

Document Type

Article

Publication Date

5-2022

Abstract

Mutant RAS proteins are associated with 30% of all human cancers. Unregulated cell growth caused by mutant RAS proteins can be prevented by RAS farnesyl protein transferase (FPTase) inhibitors. A novel FPTase inhibitor has been synthesized incorporating a modified farnesyl “tail” and a customized diphosphate “head”. It is anticipated that the modified “tail”, incorporating a phenyl substituent, will bind more tightly to FPTase due to nonbonding interactions between the aromatic ring and ten aromatic amino acid residues that line the enzyme active site. The altered polar “head”, designed from L-aspartic acid, has already been shown to mimic the natural substrate’s diphosphate moiety. It is anticipated that the bioactivity of the novel compound presented in this research will illustrate the relevance of modifications to the farnesyl “tail” in the design of farnesyl diphosphate mimetics.

Comments

The article originally appeared in the spring 2022 issue of the Journal of Undergraduate Chemistry Research: https://www.westmont.edu/sites/default/files/2022-05/Mark%20Mechelke_final.pdf

Recommended Citation

Mechelke, Mark F. and Mikolchak, Anna, "Synthesis of a Novel RAS Farnesyl Protein Transferase Inhibitor" (2022). Chemistry Faculty Publications. 11.
https://repository.stcloudstate.edu/chem_facpubs/11