RESUMO
While chitooligosaccharides (COs) derived from fungal chitin are potent elicitors of defense reactions, structurally related signals produced by certain bacteria and fungi, called lipo-chitooligosaccharides (LCOs), play important roles in the establishment of symbioses with plants. Understanding how plants distinguish between friend and foe through the perception of these signals is a major challenge. We report the synthesis of a range of COs and LCOs, including photoactivatable probes, to characterize a membrane protein from the legume Medicago truncatula. By coupling photoaffinity labeling experiments with proteomics and transcriptomics, we identified the likely LCO-binding protein as LYR3, a lysin motif receptor-like kinase (LysM-RLK). LYR3, expressed heterologously, exhibits high-affinity binding to LCOs but not COs. Homology modeling, based on the Arabidopsis CO-binding LysM-RLK AtCERK1, suggests that LYR3 could accommodate the LCO in a conserved binding site. The identification of LYR3 opens up ways for the molecular characterization of LCO/CO discrimination.
Assuntos
Quitina/análogos & derivados , Medicago truncatula/fisiologia , Oligossacarídeos/metabolismo , Proteínas de Plantas/metabolismo , Sequência de Aminoácidos , Lipídeos/química , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Oligossacarídeos/química , Proteínas de Plantas/química , Alinhamento de Sequência , SimbioseRESUMO
Promising synthetic derivatives of macrolactone natural product (-)-A26771B have been designed and synthesized both from semisynthesis and total synthesis. Further optimization led to the first synthesis of macrolactam analogs of (-)-A26771B with improved antibacterial activity and metabolic stability.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Fatores Biológicos/farmacologia , Antibacterianos/síntese química , Antibacterianos/metabolismo , Fatores Biológicos/síntese química , Fatores Biológicos/metabolismo , Relação Dose-Resposta a Droga , Desenho de Fármacos , Lactonas/síntese química , Lactonas/metabolismo , Lactonas/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
[structure: see text] Hsp90 has recently emerged as a promising biological target for treatment of cancer. Herbimycin A and other members of the benzoquinoid ansamycin class of natural products are known to inhibit Hsp90 activity. The total synthesis of herbimycin A was achieved from the commercially available Roche ester 1 by using allylmetals to control the stereogenic centers at C6, C7, C10, C11, and C12 and a ring-closing metathesis to control the (Z)-double bond of the (E,Z)-dienic moiety.
Assuntos
Benzoquinonas/síntese química , Lactamas Macrocíclicas/síntese química , Benzoquinonas/química , Carbono/química , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Lactamas Macrocíclicas/química , Estrutura Molecular , Rifabutina/análogos & derivadosRESUMO
[reaction: see text] Treatment of beta,gamma-unsaturated monoprotected 1,2-diols with diethylaminosulfur trifluoride (DAST) allows the stereoselective formation of beta,gamma-unsaturated aldehydes in good yields and with a good transfer of chirality.
