I need help with understanding structural activity relationship of modified compounds.

Question

I synthesized peptoid or mimics of Wollamide a TB antibiotic. I’m seeking to determine the structural activity relationship and understand stereochemistry of each compound. I need to know what’s the mechanism of action of my compound given the modifications. I have an idea regarding the MOA, since wollamide is a cationic antimycobacterial cyclohexapeptide that exhibits activity against Mycobacterium bovis. If a cyclic peptide inhibits protein synthesis 50s of ribosome. Is it safe to assume wollamide can diffuse through the cell membrane and inhibit protein synthesis?

Answer 1

Interesting question. Based on the research articles I have reviewed, the MOA is not known and is being researched by many groups. However, studies have demonstrated that the cyclic scaffold, specific amides and amino acids, and the original stereochemistry pattern of the core scaffold are important for its antituberculosis and antibacterial activity. I have found in research it is never safe to make assumptions that are not justified. One experiment I would do is to see if the 50S ribosome interacts with Wollamide TB antibiotic.