1.Solid-Phase Total Synthesis of Bacitracin A.
Lee J1, Griffin JH, Nicas TI. J Org Chem. 1996 Jun 14;61(12):3983-3986.
An efficient solid-phase method for the total synthesis of bacitracin A is reported. This work was undertaken in order to provide a general means of probing the intriguing mode of action of the bacitracins and exploring their potential for use against emerging drug-resistant pathogens. The synthetic approach to bacitracin A involves three key features: (1) linkage to the solid support through the side chain of the L-asparaginyl residue at position 12 (L-Asn(12)), (2) cyclization through amide bond formation between the alpha-carboxyl of L-Asn(12) and the side chain amino group of L-Lys(8), and (3) postcyclization addition of the N-terminal thiazoline dipeptide as a single unit. To initiate the synthesis, Fmoc L-Asp(OH)-OAllyl was attached to a PAL resin. The chain of bacitracin A was elaborated in the C-to-N direction by sequential piperidine deprotection/HBTU-mediated coupling cycles with Fmoc D-Asp(OtBu)-OH, Fmoc L-His(Trt)-OH, Fmoc D-Phe-OH, Fmoc L-Ile-OH, Fmoc D-Orn(Boc)-OH, Fmoc L-Lys(Aloc)-OH, Fmoc L-Ile-OH, Fmoc D-Glu(OtBu)-OH, and Fmoc L-Leu-OH.
2.Identification and synthesis of a novel selective partial PPARdelta agonist with full efficacy on lipid metabolism in vitro and in vivo.
Sauerberg P1, Olsen GS, Jeppesen L, Mogensen JP, Pettersson I, Jeppesen CB, Daugaard JR, Galsgaard ED, Ynddal L, Fleckner J, Panajotova V, Polivka Z, Pihera P, Havranek M, Wulff EM. J Med Chem. 2007 Apr 5;50(7):1495-503. Epub 2007 Mar 8.
The aim was to identify a novel selective PPARdelta agonist with full efficacy on free fatty acid (FFA) oxidation in vitro and plasma lipid correction in vivo. Using the triple PPARalpha,gamma,delta agonist 1 as the structural starting point, we wanted to investigate the possibility of obtaining selective PPARdelta agonists by modifying only the acidic part of 1, while holding the lipophilic half of the molecule constant. The structure-activity relationship was guided by in vitro transactivation data using the human PPAR receptors, FFA oxidation efficacy performed in the rat muscle L6 cell line, and in vivo rat pharmacokinetic properties. Compound 7 ([4-[3,3-bis-(4-bromo-phenyl)-allylthio]-2-chloro-phenoxy]-acetic acid) was identified as a selective, partial agonist with good oral pharmacokinetic properties in rat. Chronic treatment of high fat fed ApoB100/CETP-Tgn mice with 7 corrected the plasma lipid parameters and improved insulin sensitivity.
3.Development of antimicrobial coatings for improving the microbiological safety and quality of shell eggs.
Jin TZ1, Gurtler JB, Li SQ. J Food Prot. 2013 May;76(5):779-85. doi: 10.4315/0362-028X.JFP-12-460.
This study was conducted to develop antimicrobial coatings to decontaminate and prevent cross-contamination of shell eggs. Egg shells were inoculated with nalidixic acid-resistant Salmonella enterica Enteritidis strains OB030832, OB040159, and C405 and treated with antimicrobial coatings. Polylactic acid served as a nonedible polymer, and chitosan served as an edible polymer carrier of natural antimicrobials, including nisin, allyl isothiocyanate (AIT), lauric arginate ester (LAE), and organic acids. Increases of AIT concentrations or addition of nisin to AIT in either the polylactic acid or chitosan coating solutions resulted in greater reductions of Salmonella. Chitosan coatings with 0.1, 0.5, and 1.0% LAE reduced Salmonella by 1.7, 2.5, and 5.2 log CFU/cm(2), respectively. Shell eggs treated with 1.0 and 0.5% LAE in chitosan coatings had nondetectable Salmonella cells (< 0.5 log CFU/cm(2)) after 3 and 7 days of storage at 7°C, respectively, and no outgrowth was observed up to 28 days.
4.Modulation of protein fermentation does not affect fecal water toxicity: a randomized cross-over study in healthy subjects.
Windey K1, De Preter V, Louat T, Schuit F, Herman J, Vansant G, Verbeke K. PLoS One. 2012;7(12):e52387. doi: 10.1371/journal.pone.0052387. Epub 2012 Dec 20.
OBJECTIVE: Protein fermentation results in production of metabolites such as ammonia, amines and indolic, phenolic and sulfur-containing compounds. In vitro studies suggest that these metabolites might be toxic. However, human and animal studies do not consistently support these findings. We modified protein fermentation in healthy subjects to assess the effects on colonic metabolism and parameters of gut health, and to identify metabolites associated with toxicity.