Definition: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
Input: Inhibitors of bacterial DD-peptidases represent potential antibiotics. In the search for alternatives to β-lactams, we have investigated a series of compounds designed to generate transition state analogue structures on reaction with DD-peptidases. The compounds contain a combination of a peptidoglycan-mimetic specificity handle and a warhead capable of delivering a tetrahedral anion to the enzyme active site. The latter include a boronic acid, two alcohols, an aldehyde and a trifluoroketone. The compounds were tested against two low molecular mass class C DDpeptidases. As expected from previous observations, the boronic acid was a potent inhibitor, but, rather unexpectedly from precedent, the trifluoroketone [D-α-aminopimelyl-(1,1,1-trifluoro-3amino)butan-2-one] was also very effective. Taking into account competing hydration, the trifluoroketone was the strongest inhibitor of the Actinomadura R39 DD-peptidase, with a subnanomolar (free ketone) inhibition constant. A crystal structure of the complex between the trifluoroketone and the R39 enzyme showed that a tetrahedral adduct had indeed formed with the active site serine nucleophile. The trifluoroketone moiety, therefore, should be considered along with boronic acids and phosphonates, as a warhead that can be incorporated into new and effective DD-peptidase inhibitors and therefore, perhaps, antibiotics. The bacterial DD-peptidases are of considerable importance in medical practice since they are the targets of β-lactam antibiotics. (1) These enzymes catalyze the final transpeptidation reaction in the biosynthesis of bacterial cell walls and are essential to bacterial survival. The β-lactams, acting as mechanism-based/transition state analogue inhibitors (2-4), are precisely structured to inactivate DD-peptidases in a manner that these enzymes have been unable to escape through evolution of a hydrolytic pathway. Bacteria have, however, been able to achieve resistance to β-lactams in a number of ways unrelated to DD-peptidase active site structure, and, in particular through evolution of β-lactamases from DD-peptidases (2,4). The β-lactamases, unlike DD-peptidases, are able to catalyze rapid β-lactam hydrolysis and thus destruction of their antibiotic activity (5).

Inhibition of DD-Peptidases by a Specific Trifluoroketone: Crystal Structure of a Complex with the Actinomadura R39 DD- Peptidase † NIH Public Access Author Manuscript