Professor of Chemistry Emeritus Robin Kinnel recently published research involving new methodologies for discovery of natural products with potential biological activity on the American Chemical Society website.
The online article, “A Maldiisotopic Approach to Discover Natural Products: Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens,” describes culturing organisms with heavy nitrogen, followed by mass spectrometry analysis of the cyanobacterium to reveal compounds that incorporate one or more nitrogens.
Since a large majority of naturally occurring therapeutically active materials contain nitrogen, this technique can uncover hitherto undiscovered substances that were not detected earlier, either because the screening protocols weren’t sensitive enough or too directed to reveal them. It is clear from genome sequencing of a variety of microorganisms that they have greater capacity for natural products biosynthesis than was previously recognized.
Application of the technique to the cyanobacterium Moorea producens, originally collected in Jamaica, revealed the presence of several known compounds as well as a new one that incorporated five nitrogen atoms.
Termed “cryptomaldamide” because it was originally hidden but revealed by MALDI mass spectrometry, the substance was isolated and its structure was established as a tripeptide with two of the three amino acids considerably modified.
Although the compound had very low cytotoxicity, its structure in part compares to powerfully anticancer substances.
The Kinnel group is currently synthesizing congeners for biological testing and hopes that these will provide leads to viable drug candidates.
