OF-1

OF-1 is a selective BRPF1B and BRPF2 bromodomain inhibitor (Kd value = 100nM and 500 nM, respectively; >100-fold selectivity over majority of other bromodomains).
BRPF (BRomodomain and PHD Finger containing) protein family are scaffolding proteins that assembles MYST histone acetyltransferase complexes. MYST complexes play important role in DNA repair, recombination, replication and transcription activation.
In cellular thermal shift assay (CETSA) of full length BRPF1B, OF-1 enhanced thermal stability at 1 µM. In BRPF2 FRAP assay, OF-1 showed accelerated FRAP recovery at 5µM. OF-1 exhibited modest general cytotoxicity.
References:
[1]. OF-1 - A chemical probe for BRPF bromodomains. (2010, October 13). SGC. Retrieved from http://www.thesgc.org/chemical-probes/OF-1

A formal intermolecular [4 + 2] cycloaddition reaction of 1,3-disubstituted indoles and alkylquinones.[Pubmed:28379272]

Org Biomol Chem. 2017 Apr 18;15(16):3472-3478.

A formal [4 + 2] cycloaddition reaction of 1,3-disubstituted indoles and alkylquinones was realized to furnish polycyclic indolines in good yields. This protocol proceeded smoothly under basic conditions, with high atom-economy and broad substrate scope.

Donor Promiscuity of a Thermostable Transketolase by Directed Evolution: Efficient Complementation of 1-Deoxy-d-xylulose-5-phosphate Synthase Activity.[Pubmed:28378514]

Angew Chem Int Ed Engl. 2017 May 2;56(19):5358-5362.

Enzymes catalyzing asymmetric carboligation reactions typically show very high substrate specificity for their nucleophilic donor substrate components. Structure-guided engineering of the thermostable transketolase from Geobacillus stearothermophilus by directed in vitro evolution yielded new enzyme variants that are able to utilize pyruvate and higher aliphatic homologues as nucleophilic components for acyl transfer instead of the natural polyhydroxylated ketose phosphates or hydroxypyruvate. The single mutant H102T proved the best hit toward 3-methyl-2-oxobutyrate as donor, while the double variant H102L/H474S showed highest catalytic efficiency toward pyruvate as donor. The latter variant was able to complement the auxotrophic deficiency of Escherichia coli cells arising from a deletion of the dxs gene, which encodes for activity of the first committed step into the terpenoid biosynthesis, offering the chance to employ a growth selection test for further enzyme optimization.

Culture Clash? Investigating constructions of sexual and reproductive health from the perspective of 1.5 generation migrants in Australia using Q methodology.[Pubmed:28376911]

Reprod Health. 2017 Apr 4;14(1):50.

BACKGROUND: In Australia, those who migrate as children or adolescents (1.5 generation migrants) may have entered a new cultural environment at a crucial time in their psychosexual development. These migrants may have to contend with constructions of sexual and reproductive health from at least two cultures which may be at conflict on the matter. This study was designed to investigate the role of culture in constructions of sexual and reproductive health and health care seeking behaviour from the perspective of 1.5 generation migrants. METHODS: Forty-two adults from various ethno-cultural backgrounds took part in this Q methodological study. Online, participants rank-ordered forty-two statements about constructions of sexual and reproductive health and health seeking behaviours based on the level to which they agreed or disagreed with them. Participants then answered a series of questions about the extent to which their ethnic/cultural affiliations influenced their identity. A by-person factor analysis was then conducted, with factors extracted using the centroid technique and a varimax rotation. RESULTS: A seven-factor solution provided the best conceptual fit for constructions of sexual and reproductive health and help-seeking. Factor A compared progressive and traditional sexual and reproductive health values. Factor B highlighted migrants' experiences through two cultural lenses. Factor C explored migrant understandings of sexual and reproductive health in the context of culture. Factor D explained the role of culture in migrants' intimate relationships, beliefs about migrant sexual and reproductive health and engagement of health care services. Factor E described the impact of culture on sexual and reproductive health related behaviour. Factor F presented the messages migrant youth are given about sexual and reproductive health. Lastly, Factor G compared constructions of sexual and reproductive health across cultures. CONCLUSIONS: This study has demonstrated that when the cultural norms of migrants' country of origin are maintained it has a significant influence on how 1.5 generation migrants construct, experience and understand various aspects of sexual and reproductive health. Policy makers, health care professionals and resettlement service providers are advised to engage with migrant parents and youth in exploring, discussing, reframing and reconstructing SRH in an Australian context.

Usefulness of 1,3 Beta-D-Glucan Detection in non-HIV Immunocompromised Mechanical Ventilated Critically Ill Patients with ARDS and Suspected Pneumocystis jirovecii Pneumonia.[Pubmed:28378239]

Mycopathologia. 2017 Aug;182(7-8):701-708.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PCP) is a major cause of disease in immunocompromised individuals. Diagnosis is typically obtained by microscopy and/or PCR. For ambiguous PCR results, we evaluated the new biomarker 1,3-Beta-D-Glucan (BDG). METHODS: BDG serum levels were assessed and correlated to PCR results in immunosuppressed patients with ARDS. RESULTS: 11 (22%) out of 50 patients had suspected PCP. APACHE II (26 vs. 24; p < 0.002), SOFA score (16 vs. 14; p < 0.010) and mortality rate (34 vs. 69% p < 0.004; 34 vs. 80% p < 0.003) were significantly altered in patients with positive (pPCR) and slightly positive (spPCR) PCJ PCR as compared to patients with no-PCP (nPCP). BDG levels were significantly lower in patients with nPCP (86; 30-315 pg/ml) than in patients with pPCR (589; 356-1000 pg/ml; p < 0.001) and spPCP (398; 297-516 pg/ml; p < 0.004) referring to the cutoff in this study for PCP of 275 pg/ml. An overall sensitivity (S) of 92% (95% CI 86-96%) and specificity (SP) of 84% (95% CI 79-85%) for PCP were found for the BDG Fungitell assay. In detail, S of 98% (95% CI 94-100%) and SP of 86% (95% CI 82-92%) for pPCP and S of 98% (95% CI 96-100%) and SP of 88% (95% CI 86-96%) for spPCO were found. CONCLUSION: Serum BDG levels were strongly elevated in PCP, and the negative predictive value is high. BDG could be used as a preliminary test for patients with suspected PCP, especially in patients with slightly positive PCR results.

OF-1 is a selective BRPF1B and BRPF2 bromodomain inhibitor with Kd values of 100 nM/500 nM for BRPF1B/BRPF2; 39-fold selectivity over BRD4.

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