. . "2008-12-31+01:00"^^ . "1786"^^ . "Project is aimed to synthesis and testing of inhibitors of dapE-encoded N-succinyldiaminopimelic acid desuccinylases and argE-encoded N-alpha-acetylornithine deacetylase, catalyzing a conversion to diaminopimelic acid and to ornithine in the presence of Zn(II). Inhibition of above, not in mammals found pathways, can provide selective toxicity against several bacterial strains resistant to all currently available antibiotics. Inhibitors of dapE's may thus provide a new class of antibiotics. Substrate specificity of argE's covers several N-acylamino acids that show larger antibacterial activity than N-alpha-acetylornithine. In this project, new analogs of diaminopimelic acid and ornithine with prolonged or shortened carbon chains, with amino group substitution, with insertion of alkylenediamino- or diazo-linker and cyclic analogues or those modified with isosteric structures, will be synthesized. Inhibitory potential of new compound will be assayed in cooperation with laboratory in USA."@en . "Synt\u00E9za a charakterizace nov\u00FDch potentn\u00EDch inhibitor\u016F enzym\u016F dapE a argE se selektivn\u00EDm antimikrobi\u00E1ln\u00EDm \u00FA\u010Dinkem na kmeny rezistentn\u00EDch patogenn\u00EDch bakteri\u00ED"@cs . . "3"^^ . . . . . . . "0"^^ . "Projekt je zame\u0159en na synt\u00E9zu a testov\u00E1n\u00ED inhibitor\u016F dapE-enkodovan\u00FDch desukcinyl\u00E1s N-sukcinyldiaminopimelov\u00E9 kyseliny (dapE's) a argE-enkodovan\u00FDch deacetyl\u00E1s N-alfa-acetylornithinu, katalyzuj\u00EDc\u00EDch konverzi na diaminopimelovou kyselinu a na ornithin v p\u0159\u00EDtomnosti Zn(II). Inhibice t\u011Bchto, u savc\u016F dosud nezji\u0161t\u011Bn\u00FDch pochod\u016F, m\u016F\u017Ee poskytnout selektivn\u00ED toxicitu v\u016F\u010Di n\u011Bkter\u00FDm bakteri\u00E1ln\u00EDm kmen\u016Fm, rezistentn\u00EDm v\u016F\u010Di dostupn\u00FDm antibiotik\u016Fm. Inhibitory dapE's tak mohou vytvo\u0159it novou t\u0159\u00EDdou antibiotik. Substr\u00E1tov\u00E1 specifita argE pokr\u00FDv\u00E1 n\u011Bkolik N-acylaminokyselin, kter\u00E9 vykazuj\u00ED vy\u0161\u0161\u00ED antibakteri\u00E1ln\u00ED aktivitu ne\u017E N-alfa-acetylornithin. V tomto projektu budou p\u0159ipraveny analogy diaminopimelov\u00E9 kyseliny a ornithinu s prodlou\u017Een\u00FDm nebo zkr\u00E1cen\u00FDm uhlovod\u00EDkov\u00FDm \u0159et\u011Bzcem, se substituc\u00ED aminoskupiny, s inserc\u00ED alkylendiamino- nebo diazo-spojky a analogy cyklizovan\u00E9 \u010Di upraven\u00E9 vlo\u017Een\u00EDm isostern\u00EDch struktur. Inhibi\u010Dn\u00ED potenci\u00E1l nov\u00FDch slou\u010Denin bude testov\u00E1n ve spolupr\u00E1ci s pracovi\u0161t\u011Bm v USA."@cs . "Synthesis and characterization of new potent inhibitors of enzymes dapE and argE with selective antimicrobial effect on resistant pathogenic bacterial strains"@en . "2006-01-01+01:00"^^ . "metalloproteases; inhibitors; antibiotics; amino acids derivatives; pathogenic bacteria"@en . . "1786"^^ . "1"^^ . "0"^^ . "3"^^ .