From the article above- The researchers tested these compounds...

From the article above-

The researchers tested these compounds individually against gram-negative bacteria, looking for those that successfully accumulated inside the cells.

“The few that got in all had amines on them, so we started building out from there,” Hergenrother said. Amines are molecular components that contain the element nitrogen.

The researchers tested more compounds with amines, and their success rate increased. But this was not the only trait needed to break into the gram-negative cells.

“Having an amine was necessary but not sufficient,” Hergenrother said.

Using a computational approach, the team discovered three key traits required for access: To get in, a compound must have an amine that is not hindered by other molecular components; it must be fairly rigid (floppy compounds are more likely to get stuck in the porin gateway), and it must have “low globularity,” which, more simply, means it must be flat, not fat.

To test these guidelines, the team added an amine group to deoxynybomycin, a compound created in the 1960s by Kenneth Rinehart Jr., at the time a chemistry professor at the U. of I. They chose this compound because it is a potent killer of gram-positive bacteria and has the other desirable traits: rigidity and low globularity.

By adding an amine to the right place on the molecule, the researchers converted DNM into a broad-spectrum antibiotic that they are calling 6DNM-amine.

“The point is not necessarily this compound, which may or may not be a good candidate as a drug used in human health,” Hergenrother said. “It’s more important as a demonstration that we understand the fundamentals at play here. Now, we know how to make collections of compounds where everything gets in.”

Finding compounds that penetrate the membrane is important, but antibiotics also must kill the bacteria. Previous research suggests that only about one in 200 random compounds that penetrate gram-negative bacteria are also likely to kill the bacteria, Hergenrother said.

“These are workable odds,” he said. “Much better than zero in 500,000.”





It would be good if we can add more phylomer to our library that actually have an "amine" and then attach to deoxynybomycin or similar. Maybe we could then kill a whole lot of other gram negative bacteria?? I wonder if pyc are aware of this or are just using whatever comes up on a scan. I guess the libraries are so diverse maybe they are getting hits with phylomer that have amines without even knowing it??