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1.
Med Sci Law ; : 258024211053977, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34796760

RESUMO

Awareness of the nature and frequency of complaints against health care professionals working in police custodial health care services could provide opportunities to improve patient safety. To explore this freedom of information requests were sent to police services in England, Wales and Northern Ireland, to professional regulatory bodies and to the Independent Office for Police Conduct. Eighty-seven percent of police services responded but only a minority provided complete responses, with data not being held, or not being held in an easily retrievable format, being provided as reasons. The nature and frequency of complaints were similar to a previous 2017 study, suggesting a failure to learn lessons from the investigation of complaints and implement change in clinical practice. No evidence of an accessible complaints handling and recording procedure was provided across the police services surveyed. Regulatory bodies provided some information on the nature of complaints made against doctors and nurses working in police custodial settings, but that for paramedics was unable to do so. It is recommended that the communication loop between police services, those bodies providing health care and forensic medical services and regulatory bodies needs to be closed. A common reporting system or the application of established complaints handling procedures and reporting structures, which could be achieved by transferring these services to the National Health Service, may enhance patient safety in police custody.

2.
Forensic Sci Int ; 327: 110962, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34474199

RESUMO

INTRODUCTION: Most findings of forensic pathology examinations are presented as written reports. There are currently no internationally accepted recommendations for writing forensic pathology reports. Existing recommendations are also varied and reflect the differences in the scope and role of forensic medical services and local settings in which they are to be implemented. The legal fact-finder thus faces wide variation in the quality of forensic pathology reports, which poses a threat to the reliability of legal decision-making. To address this issue, the development of the "PERFORM-P (Principles of Evidence-based Reporting in FORensic Medicine-Pathology version)" was undertaken. The goal of the PERFORM-P is to provide common practice recommendations adaptable to local requirements to promote evidence-based practice (EBP) in forensic pathology. METHODS: An international consensus study was conducted in three phases by (1) developing a long-list of items to be considered in the reporting recommendations, (2) conducting a Delphi process (an iterative survey method to transform individual opinions into group consensus) with international forensic pathologists, and (3) designing the PERFORM-P prototype and its accompanying manual. RESULTS: With assistance from 106 forensic pathologists/forensic medical practitioners from 41 countries, the PERFORM-P was developed. The PERFORM-P consists of a list of 61 items to be included in a forensic pathology report, which is accompanied by its Explanation and Elaboration (E&E) document. DISCUSSION: To prepare forensic pathology (postmortem) reports that incorporate principles of evidence-based practice, internationally accepted recommendations might be helpful. The PERFORM-P identifies recommendations for necessary elements to include in a forensic pathology report. PERFORM-P can be applied to a wide range of matters requiring forensic pathological analysis, acceptable to forensic pathologists from a representative selection of jurisdictions and medico-legal systems.


Assuntos
Consenso , Técnica Delfos , Patologia Legal/normas , Guias de Prática Clínica como Assunto/normas , Relatório de Pesquisa/normas , Adulto , Prática Clínica Baseada em Evidências , Humanos , Internacionalidade , Pessoa de Meia-Idade , Inquéritos e Questionários
3.
Thromb Res ; 202: 90-95, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33798804

RESUMO

BACKGROUND: Clinical manifestations and optimal management strategies in patients with splanchnic vein thrombosis (SVT) are not well characterized. METHODS: We conducted a retrospective cohort study including all newly diagnosed SVT evaluated between January 2007 and December 2018. Efficacy outcome was thrombosis resolution, and safety outcomes included death and occurrence of bleeding. RESULTS: We included 155 patients with a mean age of 56.2 (18-87). Local risk factors were present in 118 (76.1%) patients and 30 (19.4%) had only systemic/thrombophilia. Local risk factors included abdominal cancers (31%), surgery (20.6%) and liver cirrhosis (19.4%). Thrombophilia screening was conducted in approximately 50% of patients. Factor V Leiden or Prothrombin G20210A mutations were observed in 7.1% of patients whereas 14.4% were JAK2V617F mutation positive. Most common manifestations at onset were abdominal pain (56.1%), whereas 44.6% were incidentally found. Portal vein thrombosis was observed more in primary cases (91.9% vs. 69.5%, p = 0.012). Anticoagulation was used in 93.5% cases. Indefinite anticoagulation was used more frequently in primary SVT (62.2% vs. 41.5%, p = 0.045). Thrombosis resolution and bleeding complications among primary (without local risk factors) and secondary (with local risk factors) SVT were observed in 48.5%, 65%, 8.1%, and 11.9%, respectively with no difference when comparing patients treated with direct oral anticoagulants or warfarin and/or low molecular weight heparin (58% vs. 62%, p = 0.326, 9% vs. 12%, p = 0.518). CONCLUSIONS: In this cohort anticoagulation resulted in partial or complete thrombosis resolution in a significant proportion of patients with an acceptable bleeding risk regardless local risk factors or type of anticoagulant.


Assuntos
Circulação Esplâncnica , Trombose Venosa , Anticoagulantes/uso terapêutico , Humanos , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico
4.
Nat Commun ; 12(1): 1760, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741955

RESUMO

Plant natural products (PNPs) and their derivatives are important but underexplored sources of pharmaceutical molecules. To access this untapped potential, the reconstitution of heterologous PNP biosynthesis pathways in engineered microbes provides a valuable starting point to explore and produce novel PNP derivatives. Here, we introduce a computational workflow to systematically screen the biochemical vicinity of a biosynthetic pathway for pharmaceutical compounds that could be produced by derivatizing pathway intermediates. We apply our workflow to the biosynthetic pathway of noscapine, a benzylisoquinoline alkaloid (BIA) with a long history of medicinal use. Our workflow identifies pathways and enzyme candidates for the production of (S)-tetrahydropalmatine, a known analgesic and anxiolytic, and three additional derivatives. We then construct pathways for these compounds in yeast, resulting in platforms for de novo biosynthesis of BIA derivatives and demonstrating the value of cheminformatic tools to predict reactions, pathways, and enzymes in synthetic biology and metabolic engineering.


Assuntos
Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Biologia Computacional/métodos , Engenharia Metabólica/métodos , Noscapina/metabolismo , Saccharomyces cerevisiae/metabolismo , Alcaloides/biossíntese , Benzilisoquinolinas/metabolismo , Noscapina/química , Plantas/genética , Plantas/metabolismo , Saccharomyces cerevisiae/genética , Software
5.
Thromb Res ; 197: 8-12, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33160117

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a significant public health concern that carries high rates of morbidity and mortality. To date, limited epidemiological data are available. We conducted a meta-analysis of three epidemiological studies in Canada to determine an estimate of the national VTE incidence rate. METHODS: We used data from three large studies that looked at acute VTE incidence in three of Canada's largest provinces. Patients in each of the concurrent studies were identified using various provincial health databases. Patients with previous diagnosis of VTE (prevalent VTE) were excluded. Age- and sex-specific data were combined using a generic inverse variance method to produce an estimate for the total VTE incidence rate for the three provinces, as well as estimates by age group and sex. RESULTS: Studies included 113,171,431 patient-years of observation and 144,906 newly diagnosed VTE events. The meta-analysis resulted in a combined incidence rate (IR) of 1.29 acute VTE events per 1000 person-years (95% CI 1.06-1.53). Among men (55,415,674 observed person-years and 63,246 events), the IR was 1.13 (95% CI 0.91-1.36), and among women (57,755,755 observed person-years and 81,660 events) it was 1.44 (95% CI 1.19-1.69). Higher VTE incidence was observed in females and the IR consistently increased with age. CONCLUSION: This study provides a current estimate of VTE incidence in Canada. The results were in line with estimates obtained from studies in other jurisdictions and confirming higher incidence of VTE in females and in the elderly.


Assuntos
Tromboembolia Venosa , Trombose Venosa , Idoso , Canadá/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Fatores de Risco , Tromboembolia Venosa/epidemiologia
6.
Environ Sci Pollut Res Int ; 28(26): 33751-33763, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32556995

RESUMO

This exploratory study extends the literature on the convergence of per capita carbon dioxide emissions in analyzing stochastic and club convergence within a panel framework for developing countries. The results from Pesaran (Journal of Applied Econometrics, 22(2), 265-312, 2007) and Bai and Carrion-i-Silvestre (Review of Economic Studies, 76(2), 471-501, 2009) panel unit root tests with allowance for cross-sectional dependence confirm stochastic convergence for low-income, lower middle-income, and combined country panels. Further analysis using the nonlinear time-varying factor model of Phillips and Sul (Econometrica, 75(6), 1771-1855, 2007; Journal of Applied Econometrics, 24(7), 1153-1185, 2009) to test for convergence reveals the emergence of multiple convergence clubs within each of the three country panels examined. We observe geographic proximity among many of the countries within the respective convergence clubs.


Assuntos
Dióxido de Carbono , Países em Desenvolvimento , Estudos Transversais , Desenvolvimento Econômico , Renda , Organizações
7.
Urol Case Rep ; 34: 101472, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33204640

RESUMO

Retroperitoneal foreign bodies are rare indications for exploratory surgery. We present a case of a 19-year-old male with abdominal pain after a fall who was found to have a linear metallic object adjacent to the right ureter and inferior vena cava. Given the patient's pain and discomfort, he elected for robotic exploration of the retroperitoneum, which was carried out successfully with the Da Vinci Si® robot. This case demonstrates the feasibility of robotic retroperitoneal exploration and foreign body retrieval for a very small object.

8.
Torture ; 30(1): 66-78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32657772

RESUMO

Conversion therapy is a set of practices that aim to change or alter an individual's sexual orientation or gender identity. It is premised on a belief that an individual's sexual orientation or gender identity can be changed and that doing so is a desirable outcome for the individual, family, or community. Other terms used to describe this practice include sexual orientation change effort (SOCE), reparative therapy, reintegrative therapy, reorientation therapy, ex-gay therapy, and gay cure. Conversion therapy is practiced in every region of the world. We have identified sources confirming or indicating that conversion therapy is performed in over 60 countries. In those countries where it is performed, a wide and variable range of practices are believed to create change in an individual's sexual orientation or gender identity. Some examples of these include: talk therapy or psychotherapy (e.g., exploring life events to identify the cause); group therapy; medication (including anti-psychotics, anti- depressants, anti-anxiety, and psychoactive drugs, and hormone injections); Eye Movement Desensitization and Reprocessing (where an individual focuses on a traumatic memory while simultaneously experiencing bilateral stimulation); electroshock or electroconvulsive therapy (ECT) (where electrodes are attached to the head and electric current is passed between them to induce seizure); aversive treatments (including electric shock to the hands and/or genitals or nausea-inducing medication administered with presentation of homoerotic stimuli); exorcism or ritual cleansing (e.g., beating the individual with a broomstick while reading holy verses or burning the individual's head, back, and palms); force-feeding or food deprivation; forced nudity; behavioural conditioning (e.g., being forced to dress or walk in a particular way); isolation (sometimes for long periods of time, which may include solitary confinement or being kept from interacting with the outside world); verbal abuse; humiliation; hypnosis; hospital confinement; beatings; and "corrective" rape. Conversion therapy appears to be performed widely by health professionals, including medical doctors, psychiatrists, psychologists, sexologists, and therapists. It is also conducted by spiritual leaders, religious practitioners, traditional healers, and community or family members. Conversion therapy is undertaken both in contexts under state control, e.g., hospitals, schools, and juvenile detention facilities, as well as in private settings like homes, religious institutions, or youth camps and retreats. In some countries, conversion therapy is imposed by the order or instructions of public officials, judges, or the police. The practice is undertaken with both adults and minors who may be lesbian, gay, bisexual, trans, or gender diverse. Parents are also known to send their children back to their country of origin to receive it. The practice supports the belief that non-heterosexual orientations are deviations from the norm, reflecting a disease, disorder, or sin. The practitioner conveys the message that heterosexuality is the normal and healthy sexual orientation and gender identity. The purpose of this medico-legal statement is to provide legal experts, adjudicators, health care professionals, and policy makers, among others, with an understanding of: 1) the lack of medical and scientific validity of conversion therapy; 2) the likely physical and psychological consequences of undergoing conversion therapy; and 3) whether, based on these effects, conversion therapy constitutes cruel, inhuman, or degrading treatment or torture when individuals are subjected to it forcibly2 or without their consent. This medico-legal statement also addresses the responsibility of states in regulating this practice, the ethical implications of offering or performing it, and the role that health professionals and medical and mental health organisations should play with regards to this practice. Definitions of conversion therapy vary. Some include any attempt to change, suppress, or divert an individual's sexual orientation, gender identity, or gender expression. This medico-legal statement only addresses those practices that practitioners believe can effect a genuine change in an individual's sexual orientation or gender identity. Acts of physical and psychological violence or discrimination that aim solely to inflict pain and suffering or punish individuals due to their sexual orientation or gender identity, are not addressed, but are wholly condemned. This medico-legal statement follows along the lines of our previous publications on Anal Examinations in Cases of Alleged Homosexuality1 and on Forced Virginity Testing.2 In those statements, we opposed attempts to minimise the severity of physical and psychological pain and suffering caused by these examinations by qualifying them as medical in nature. There is no medical justification for inflicting on individuals torture or other cruel, inhuman, or degrading treatment or punishment. In addition, these statements reaffirmed that health professionals should take no role in attempting to control sexuality and knowingly or unknowingly supporting state-sponsored policing and punishing of individuals based on their sexual orientation or gender identity.


Assuntos
Terapia Aversiva/métodos , Identidade de Gênero , Punição , Comportamento Sexual , Tortura , Fármacos do Sistema Nervoso Central , Consenso , Eletroconvulsoterapia , Feminino , Humanos , Masculino , Psicoterapia
10.
J Forensic Leg Med ; 66: 147-154, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31306914

RESUMO

Spit guards, also known as spit hoods or spit masks (and occasionally bite guards) are devices intended to cover the mouth, face and sometimes the head of a restrained person in order to prevent them spitting at, or biting others. There is substantial controversy about their use with views often polarised between civil and human rights campaigners who express concerns about their utility, their safety, and their possible encroachment on human rights, and in contrast by (predominantly) law enforcement campaigners highlighting concerns about the possible risks of transmission of infection and subsequent need for prophylaxis by law enforcement professionals exposed to biological fluids. This study explored the extent to which police services deploy spit guards and the rationale underpinning their use. A mixed qualitative and quantitative approach was used to analyse data obtained from police services under the Freedom of Information Act. This study shows there is paucity of information readily available from police services in respect of quantifying the numbers of police officers who have contracted infectious disease as a result of spitting and/or bites, despite the fact that risk of infection and the need for subsequent prophylaxis is a driver of police services adopting the use of spit guard devices. Consideration must be afforded to the possibility that the use of spit guards represents a form of mechanical restraint rather than a means to prevent transmission of infection, especially given the paucity of information available from police services in respect of officers who have contracted infectious disease as a result of spiting and/or bites.


Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Doenças Profissionais/prevenção & controle , Equipamento de Proteção Individual , Polícia , Mordeduras Humanas/prevenção & controle , Inglaterra , Humanos , Irlanda do Norte , Saliva , País de Gales
11.
Nat Commun ; 10(1): 2142, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086174

RESUMO

Metabolic engineers endeavor to create a bio-based manufacturing industry using microbes to produce fuels, chemicals, and medicines. Plant natural products (PNPs) are historically challenging to produce and are ubiquitous in medicines, flavors, and fragrances. Engineering PNP pathways into new hosts requires finding or modifying a suitable host to accommodate the pathway, planning and implementing a biosynthetic route to the compound, and discovering or engineering enzymes for missing steps. In this review, we describe recent developments in metabolic engineering at the level of host, pathway, and enzyme, and discuss how the field is approaching ever more complex biosynthetic opportunities.


Assuntos
Produtos Biológicos/metabolismo , Engenharia Metabólica/métodos , Microrganismos Geneticamente Modificados/metabolismo , Plantas/metabolismo , Vias Biossintéticas/genética , Enzimas/genética , Enzimas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Engenharia Metabólica/tendências , Microrganismos Geneticamente Modificados/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Biologia Sintética/métodos , Biologia Sintética/tendências
12.
Urology ; 128: 84-86, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30904639

RESUMO

Paratesticular masses are a relatively common finding in males. The majority are benign, as opposed to testis masses, which tend to be malignant. Fibrous pseudotumors are rare, but are the third most common paratesticular tumor after adenomatoid and lipoma. The exact cause is unclear but likely from a fibroinflammatory reaction. Because of the non-specific findings on physical exam and scrotal ultrasound, patients may undergo scrotal exploration and occasionally orchiectomy, in spite of the benign nature of this lesion. Here we report the rare case of free-floating paratesticular calcifying fibrous pseudotumors in a prepubertal patient.


Assuntos
Calcinose/diagnóstico , Fibrose/diagnóstico , Doenças Testiculares/diagnóstico , Ultrassonografia/métodos , Calcinose/cirurgia , Criança , Fibrose/cirurgia , Humanos , Masculino , Orquiectomia , Escroto , Doenças Testiculares/cirurgia
13.
Int J Legal Med ; 133(1): 317-322, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29951880

RESUMO

Article 25 of the Charter of Fundamental Rights of the European Union (adopted in Nice on 7 December 2000) recognizes and respects the rights of older people to lead a life of dignity and independence and to participate in social and cultural life. It also highlights the importance of prevention and recognition of elder abuse, especially since exposure to violence is likely as the population ages, either in familial or in institutional settings. Elder abuse has some issues in common with child abuse but in spite of this fact currently is less recognized. Health professionals have a major role to play in early detection and management of cases of elder abuse. This protocol summarizes some key concepts and approaches to assist in the timely detection and investigation of elder abuse cases by healthcare professionals and forensic practitioners.


Assuntos
Abuso de Idosos/diagnóstico , Abuso de Idosos/legislação & jurisprudência , Idoso , Europa (Continente) , Avaliação Geriátrica , Humanos , Consentimento Livre e Esclarecido , Anamnese , Inquéritos e Questionários
14.
J Forensic Leg Med ; 57: 58-65, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29801954

RESUMO

Death and harm is well-recognised in detainees in police custody worldwide. Based on the results of previous global surveys and the CPT (European Committee for the Prevention of Torture) recommendations a questionnaire was developed to summarise the current medical aspects of police custody in European countries. The survey was distributed to named contacts in all European countries. Data from 25 European countries was obtained. The results reveal significant differences in the regulations among the different countries, with nothing close to a harmonised European standard in place at present. This study has identified interesting variations in the methods and standards of healthcare and forensic medical services to detainees in police custody (e.g. quantitative mode of monitoring, qualification of the doctors, maximum time allowed for holding a detainee in police custody, body or an organisation that investigates complaints against the police). There are both very detailed legal regulations in some countries while in others there are only generally observed provisions that sometimes are only given in the form of recommendations. A multinational, multiprofessional expert group is required to identify best practices, recommend basic standards of care and identify qualifications which would be appropriate for healthcare professionals working in this field.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Prisioneiros , Atenção à Saúde/normas , Europa (Continente) , Humanos , Polícia , Inquéritos e Questionários
15.
J Forensic Leg Med ; 57: 66-72, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29801955

RESUMO

The care of detainees (prisoners) in police custody has had much focus in recent years. The nature of the role of the doctor or other healthcare professionals within the police custodial setting may often be subject to conflicts, but their respective duties as healthcare professionals should generally overide any police or forensic issue that may be relevant. The laws or rules or statute that govern doctor, nurse or paramedic practice may vary from country to country, but the broad principles of healthcare ethics are universal and have been formulated not only by national healthcare regulatory bodies but by international organizations such as the World Medical Association. This article discusses in particular the duties of consent and confidentiality within the police custodial setting, giving examples of where conflicts may arise, and how they should be dealt with.


Assuntos
Confidencialidade , Consentimento Livre e Esclarecido , Polícia , Prisioneiros , Códigos de Ética , Confidencialidade/legislação & jurisprudência , Revelação/legislação & jurisprudência , Responsabilidade pela Informação/legislação & jurisprudência , Europa (Continente) , Humanos , Consentimento Livre e Esclarecido/legislação & jurisprudência , Notificação de Abuso , Competência Mental/legislação & jurisprudência , Exame Físico
16.
Mar Pollut Bull ; 129(1): 399-411, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29680565

RESUMO

Forensic chemistry assessments documented the presence of Macondo (MC252) oil from the Deepwater Horizon (DWH) spill in offshore water samples collected under Natural Resource Damage Assessment (NRDA) protocols. In ocean depths, oiled water was sampled, observed, photographed, and tracked in dissolved oxygen (DO) and fluorometry profiles. Chemical analyses, sensor records, and observations confirmed the shifting, rising oil plume above the wellhead while smaller, less buoyant droplets were entrapped in a layer at ~1000-1400 m and advected up to 412 km southwest. Near-surface oil samples showed substantial dissolution weathering from oil droplets rising through the water column, as well as enhanced evaporative losses of lighter n-alkanes and aromatic hydrocarbons. Dispersant effects from surface applications and injected at the wellhead were seen in oil profiles as enhanced weathering patterns (increased dissolution), thus implying dispersants were a functionally effective mediation treatment. Forensic assessment methods are detailed in the Supplemental information (SI).


Assuntos
Monitoramento Ambiental/métodos , Poluição por Petróleo/análise , Petróleo/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Água do Mar/química , Poluentes Químicos da Água/análise , Golfo do México
17.
Mar Pollut Bull ; 129(1): 412-419, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29540264

RESUMO

During the Deepwater Horizon blowout, unprecedented volumes of dispersant were applied both on the surface and at depth. Application at depth was intended to disperse the oil into smaller microdroplets that would increase biodegradation and also reduce the volumes buoyantly rising to the surface, thereby reducing surface exposures, recovery efforts, and potential stranding. In forensically examining 5300 offshore water samples for the Natural Resource Damage Assessment (NRDA) effort, profiles of deep-plume oil droplets (from filtered water samples) were compared with those also containing dispersant indicators to reveal a previously hypothesized but undocumented, accelerated dissolution of the polycyclic aromatic hydrocarbons (PAH) in the plume samples. We interpret these data in a fate-and-transport context and conclude that dispersant applications were functionally effective at depth.


Assuntos
Conservação dos Recursos Hídricos/métodos , Poluição por Petróleo/análise , Petróleo/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Tensoativos/química , Poluentes Químicos da Água/análise , Biodegradação Ambiental , Golfo do México , Água do Mar/química , Solubilidade
19.
J Am Chem Soc ; 140(2): 546-549, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29294291

RESUMO

Extensive effort has been devoted to engineering flavin-dependent halogenases (FDHs) with improved stability, expanded substrate scope, and altered regioselectivity. Here, we show that variants of rebeccamycin halogenase (RebH) catalyze enantioselective desymmetrization of methylenedianilines via halogenation of these substrates distal to their pro-stereogenic center. Structure-guided engineering was used to increase the conversion and selectivity of these reactions, and the synthetic utility of the halogenated products was shown via conversion of to a chiral α-substituted indole. These results constitute the first reported examples of asymmetric catalysis by FDHs.


Assuntos
Compostos de Anilina/química , Cloreto de Metileno/química , Catálise , Flavinas/química , Halogenação , Estrutura Molecular , Engenharia de Proteínas , Estereoisomerismo
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