4412-16-2Relevant articles and documents
Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analogues
An, Shi-qi,Murtagh, Julie,Twomey, Kate B.,Gupta, Manoj K.,O’Sullivan, Timothy P.,Ingram, Rebecca,Valvano, Miguel A.,Tang, Ji-liang
, (2019/06/05)
Pseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics.
Synthesis and evaluation of analogues of the glycinocin family of calcium-dependent antibiotics
Corcilius, Leo,Liu, Dennis Y.,Ochoa, Jessica L.,Linington, Roger G.,Payne, Richard J.
, p. 5310 - 5320 (2018/08/03)
The glycinocins are a class of calcium-dependent, acidic cyclolipopeptide antibiotics that are structurally related to the clinically approved antibiotic daptomycin. In this article, we describe the synthesis of a small library of glycinocin analogues that differ by variation in the exocyclic fatty acyl substituent. The glycinocin analogues were screened against a panel of Gram-positive bacteria (as well as Gram-negative P. aeruginosa). These analogues exhibited similar calcium-dependent activity to the parent natural products against Gram-positive bacteria but showed no activity against P. aeruginosa. The length of the fatty acid was shown to be important for optimal biological activity, while the hybridisation at the α,β position and branching within the fatty acyl chain had only subtle effects on activity.
Allyl-Palladium-Catalyzed α,β-Dehydrogenation of Carboxylic Acids via Enediolates
Zhao, Yizhou,Chen, Yifeng,Newhouse, Timothy R.
supporting information, p. 13122 - 13125 (2017/09/13)
A highly practical and step-economic α,β-dehydrogenation of carboxylic acids via enediolates is reported through the use of allyl-palladium catalysis. Dianions underwent smooth dehydrogenation when generated using Zn(TMP)2?2 LiCl as a base in the presence of excess ZnCl2, thus avoiding the typical decarboxylation pathway of these substrates. Direct access to 2-enoic acids allows derivatization by numerous approaches.
