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1.
Org Lett ; 26(26): 5522-5527, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38900928

RESUMO

Here, we use transcriptomic data from seeds of Musella lasiocarpa to identify five enzymes involved in the formation of dihydrocurcuminoids. Characterization of the substrate specificities of the enzymes reveals two distinct dihydrocurcuminoid pathways leading to phenylphenalenones and linear diarylheptanoid derivatives, the major seed metabolites. Furthermore, we demonstrate the stepwise conversion of dihydrobisdemethoxycurcumin to the phenylphenalenone 4'-hydroxylachnanthocarpone by feeding intermediates to M. lasiocarpa root protein extract.


Assuntos
Diarileptanoides , Fenalenos , Diarileptanoides/química , Fenalenos/química , Estrutura Molecular , Sementes/química , Musa/química , Especificidade por Substrato , População do Leste Asiático
2.
Nat Commun ; 15(1): 4525, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806518

RESUMO

Medicinal compounds from plants include bicyclo[3.3.1]nonane derivatives, the majority of which are polycyclic polyprenylated acylphloroglucinols (PPAPs). Prototype molecules are hyperforin, the antidepressant constituent of St. John's wort, and garcinol, a potential anticancer compound. Their complex structures have inspired innovative chemical syntheses, however, their biosynthesis in plants is still enigmatic. PPAPs are divided into two subclasses, named type A and B. Here we identify both types in Hypericum sampsonii plants and isolate two enzymes that regiodivergently convert a common precursor to pivotal type A and B products. Molecular modelling and substrate docking studies reveal inverted substrate binding modes in the two active site cavities. We identify amino acids that stabilize these alternative binding scenarios and use reciprocal mutagenesis to interconvert the enzymatic activities. Our studies elucidate the unique biochemistry that yields type A and B bicyclo[3.3.1]nonane cores in plants, thereby providing key building blocks for biotechnological efforts to sustainably produce these complex compounds for preclinical development.


Assuntos
Hypericum , Hypericum/metabolismo , Hypericum/genética , Hypericum/química , Compostos Bicíclicos com Pontes/metabolismo , Compostos Bicíclicos com Pontes/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Simulação de Acoplamento Molecular , Floroglucinol/metabolismo , Floroglucinol/análogos & derivados , Floroglucinol/química , Alcanos/metabolismo , Alcanos/química , Domínio Catalítico , Terpenos/metabolismo , Terpenos/química , Modelos Moleculares
3.
Chem Commun (Camb) ; 56(40): 5350-5353, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32319467

RESUMO

[(Ph3P)AuPt(nbe)3][BAr4F] (nbe = norbornene) constitutes the first olefin-containing, formal Au+IPt0 complex. The unusual coordination mode and the electronic properties have been analyzed spectroscopically and by calculations. The low binding energy of the nbe ligands make this complex a valuable precursor for formal Au+IPt0 complexes and a candidate for heterobimetallic catalysis.

4.
Pediatr Gastroenterol Hepatol Nutr ; 23(1): 72-78, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31988877

RESUMO

Infantile hepatic hemangioma, the most common vascular tumor of the liver in infancy, can occur with acute postnatal liver and congestive heart failure. Nevertheless, its course is often benign, and many children can be diagnosed and treated without surgical intervention. The distinction from malignant diseases is not always easy and it not clear whether invasive procedures for diagnosis and therapy should be performed. Here we report our experiences in our Center for Pediatric Liver Disease and postulate that large studies are needed to avoid unnecessary invasive procedures for these patients in the future.

5.
Urology ; 106: 210-215, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28479479

RESUMO

OBJECTIVE: To determine success rates, predictors of recurrence, and recurrence management of patients treated for short anterior urethral strictures by direct vision internal urethrotomy (DVIU). MATERIALS AND METHODS: We identified 128 patients who underwent DVIU of the anterior urethra between December 2009 and March 2016. Follow-up was conducted by telephone interviews. Success rates were assessed by Kaplan-Meier estimators. Predictors of stricture recurrence and different further therapy strategies were identified by uni- and multivariable Cox regression analyses. RESULTS: The mean age was 63.8 years (standard deviation: 16.3) and the overall success rate was 51.6% (N = 66) at a median follow-up of 16 months (interquartile range: 6-43). Median time to stricture recurrence was six months (interquartile range: 2-12). In uni- and multivariable analyses, only repeat DVIU (hazard ratio [HR] = 1.87, 95% confidence interval (CI) = 1.13-3.11, P= .015; and HR=1.78, 95% CI = 1.05-3.03, P = .032, respectively) was a risk factor for recurrence. Of 62 patients with recurrence, 35.5% underwent urethroplasty, 29% underwent further endoscopic treatment, and 33.9% did not undergo further interventional therapy. Age (HR = 1.05, 95% CI = 1.01-1.09, P = .019) and diabetes (HR = 2.90, 95% CI = 1.02-8.26, P = .047) were predictors of no further interventional therapy. CONCLUSION: DVIU seems justifiable in short urethral strictures as a primary treatment. Prior DVIU was a risk factor for recurrence. In case of recurrence, about one-third of the patients did not undergo any further therapy. Higher age and diabetes predicted the denial of any further treatment.


Assuntos
Gerenciamento Clínico , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Estreitamento Uretral/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Reoperação , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Uretra/cirurgia , Estreitamento Uretral/diagnóstico por imagem
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