95930-16-8Relevant academic research and scientific papers
A conformationally constrained fused tricyclic nisin AB-ring system mimic toward an improved pyrophosphate binder of lipid II
Harmsen, Rianne A.G.,Ghalit, Nourdin,Kemmink, Johan,Breukink, Eefjan,Liskamp, Rob M.J.,Rijkers, Dirk T.S.
, p. 7691 - 7699 (2014)
The bacteria-specific membrane component lipid II is essential for bacterial cell wall synthesis. A tricyclic nisin mimic was designed and synthesized in which both thioether moieties were mimicked by an alkane-bridge, as well as the introduction of a third conformational constraint consisting of a macrocyclic lactam-bridge between the N-terminus and the B-ring. The newly designed tricyclic AB-ring mimic was found to bind lipid II since it was able to inhibit nisin-induced membrane leakage in a dose-dependent manner. These results imply that the tricyclic AB-ring mimic may form a novel class of lead structures for the development of nisin-based peptide antibiotics.
Transition state mimetics of the plasmodium export element are potent inhibitors of plasmepsin v from P. falciparum and P. Vivax
Sleebs, Brad E.,Gazdik, Michelle,O'Neill, Matthew T.,Rajasekaran, Pravin,Lopaticki, Sash,Lackovic, Kurt,Lowes, Kym,Smith, Brian J.,Cowman, Alan F.,Boddey, Justin A.
, p. 7644 - 7662 (2014)
Following erythrocyte invasion, malaria parasites export a catalogue of remodeling proteins into the infected cell that enable parasite development in the human host. Export is dependent on the activity of the aspartyl protease, plasmepsin V (PMV), which cleaves proteins within the Plasmodium export element (PEXEL; RxL xE/Q/D) in the parasite's endoplasmic reticulum. Here, we generated transition state mimetics of the native PEXEL substrate that potently inhibit PMV isolated from Plasmodium falciparum and Plasmodium vivax. Through optimization, we identified that the activity of the mimetics was completely dependent on the presence of P1Leu and P3Arg. Treatment of P. falciparum-infected erythrocytes with a set of optimized mimetics impaired PEXEL processing and killed the parasites. The striking effect of the compounds provides a clearer understanding of the accessibility of the PMV active site and reaffirms the enzyme as an attractive target for the design of future antimalarials.
Peptide-bond Formation, Chemoselective Acylation of Amino Acids, and Crosslinking Reaction between Amino Acids Utilizing a Functional Five-membered Heterocycle, 1,3-Thiazolidine-2-thione
Nagao, Yoshimitsu,Miyasaka, Tadayo,Seno, Kaoru,Fujita, Eiichi,Shibata, Daisuke,Doi, Etsushiro
, p. 2439 - 2446 (2007/10/02)
The monitored aminolysis of 3-acyl-1,3-thiazolidine-2-thiones has been extended to the peptide-bond formation, the chemoselective acylation of amino acids having multifunctional groups, and the crosslinking reaction between amino acids.
