Benzyl Alcohol

Tolerance to drugs that affect neural activity is mediated, in part, by adaptive mechanisms that attempt to restore normal neural excitability. Changes in the expression of ion channel genes are thought to play an important role in these neural adaptations. The slo gene encodes the pore-forming subunit of BK-type Ca(2+)-activated K(+) channels, which regulate many aspects of neural activity. Given that induction of slo gene expression plays an important role in the acquisition of tolerance to sedating drugs, we investigated the molecular mechanism of gene induction. Using chromatin immunoprecipitation followed by real-time PCR, we show that a single brief sedation with the anesthetic benzyl alcohol generates a spatiotemporal pattern of histone H4 acetylation across the slo promoter region. Inducing histone acetylation with a histone deacetylase inhibitor yields a similar pattern of changes in histone acetylation, up-regulates slo expression, and phenocopies tolerance in a slo-dependent manner. The cAMP response element binding protein (CREB) is an important transcription factor mediating experience-based neuroadaptations. The slo promoter region contains putative binding sites for the CREB transcription factor. Chromatin immunoprecipitation assays show that benzyl alcohol sedation enhances CREB binding within the slo promoter region. Furthermore, activation of a CREB dominant-negative transgene blocks benzyl alcohol-induced changes in histone acetylation within the slo promoter region, slo induction, and behavioral tolerance caused by benzyl alcohol sedation. These findings provide unique evidence that links molecular epigenetic histone modifications and transcriptional induction of an ion channel gene with a single behavioral event.

Catalytic asymmetric Tsuji-Trost benzylation is a promising strategy for the preparation of chiral benzylic compounds. However, only a few such transformations with both good yields and enantioselectivities have been achieved since this reaction was first reported in 1992, and its use in current organic synthesis is restricted. In this work, we use N-unprotected amino acid esters as nucleophiles in reactions with benzyl alcohol derivatives. A ternary catalyst comprising a chiral aldehyde, a palladium species, and a Lewis acid is used to promote the reaction. Both mono- and polycyclic benzyl alcohols are excellent benzylation reagents. Various unnatural optically active α-benzyl amino acids are produced in good-to-excellent yields and with good-to-excellent enantioselectivities. This catalytic asymmetric method is used for the formal synthesis of two somatostatin mimetics and the proposed structure of natural product hypoestestatin 1. A mechanism that plausibly explains the stereoselective control is proposed.

Lateral partitioning of proteins and lipids shapes membrane function. In model membranes, partitioning can be influenced both by bilayer-intrinsic factors like molecular composition and by bilayer-extrinsic factors such as interactions with other membranes and solid supports. While cellular membranes can departition in response to bilayer-intrinsic or -extrinsic disruptions, the mechanisms by which they partition de novo are largely unknown. The plasma membrane of Mycobacterium smegmatis spatially and biochemically departitions in response to the fluidizing agent benzyl alcohol, then repartitions upon fluidizer washout. By screening for mutants that are sensitive to benzyl alcohol, we show that the bifunctional cell wall synthase PonA2 promotes membrane partitioning and cell growth during recovery from benzyl alcohol exposure. PonA2's role in membrane repartitioning and regrowth depends solely on its conserved transglycosylase domain. Active cell wall polymerization promotes de novo membrane partitioning and the completed cell wall polymer helps to maintain membrane partitioning. Our work highlights the complexity of membrane-cell wall interactions and establishes a facile model system for departitioning and repartitioning cellular membranes.

Background/aimThe etiology of hypertension in pediatric populations is complex and multifactorial, with metabolic abnormalities playing a fundamental role in the pathogenesis of the condition. This study investigates the therapeutic effects of Benzyl alcohol (BA), identified through metabolomics analysis of pediatric hypertension serum, on Angiotensin II (Ang II)-induced vascular and renal injury in murine models.Materials and methodsMale C57BL/6 mice were used to establish a vascular remodeling model by continuous 4-week Ang II infusion using a subcutaneous osmotic pump. Bioinformatics was used to identify target metabolites. The tail artery, common carotid artery diastolic, and systolic pressures in mice were determined with a blood pressure monitor. Vascular structure changes were assessed with HE and Masson staining, while kidney pathology was examined using HE. Serum urea nitrogen, creatinine, and cystatin C levels were measured with ELISA kit.ResultsMetabolomics analysis identified metabolite BA as a potential target for hypertension management. Compared to the Ang II group, BA reduced systolic blood pressure by 11.58% and diastolic blood pressure by 14.62% in the fourth week. After sodium nitroprusside treatment, the Ang II group showed reduced vasodilation reactivity versus the control. BA significantly restored this reactivity, unlike acetylcholine. Furthermore, BA was observed to attenuate Ang II-induced vascular mediator thickening, the mediator-to-lumen ratio, and collagen deposition. Ang II administration resulted in renal structural damage and increased concentrations of urea nitrogen, creatinine, and serum cystatin C, which was reversed by BA treatment.ConclusionBA exhibits potential in enhancing the vasodilatory response, vascular remodeling, and renal injury associated with Ang II.