Medin Oligomer Membrane Pore Formation: A Potential Mechanism of Vascular Dysfunction was written by Younger, Scott;Jang, Hyunbum;Davies, Hannah A.;Niemiec, Martin J.;Garcia, Joe G. N.;Nussinov, Ruth;Migrino, Raymond Q.;Madine, Jillian;Arce, Fernando T.. And the article was included in Biophysical Journal in 2020.Synthetic Route of C39H76NO8P The following contents are mentioned in the article:
Medin, a 50-amino-acid cleavage product of the milk fat globule-EGF factor 8 protein, is one of the most common forms of localized amyloid found in the vasculature of individuals older than 50 years. Medin induces endothelial dysfunction and vascular inflammation, yet despite its prevalence in the human aorta and multiple arterial beds, little is known about the nature of its pathol. Medin oligomers have been implicated in the pathol. of aortic aneurysm, aortic dissection, and more recently, vascular dementia. Recent in vitro biomech. measurements found increased oligomer levels in aneurysm patients with altered aortic wall integrity. Our results suggest an oligomer-mediated toxicity mechanism for medin pathol. Using lipid bilayer electrophysiol., we show that medin oligomers induce ionic membrane permeability by pore formation. Pore activity was primarily observed for preaggregated medin species from the growth-phase and rarely for lag-phase species. Atomic force microscopy (AFM) imaging of medin aggregates at different stages of aggregation revealed the gradual formation of flat domains resembling the morphol. of supported lipid bilayers. Transmission electron microscopy images showed the coexistence of compact oligomers, largely consistent with the AFM data, and larger protofibrillar structures. CD spectroscopy revealed the presence of largely disordered species and suggested the presence of 尾-sheets. This observation and the significantly lower thioflavin T fluorescence emitted by medin aggregates compared to amyloid-尾 fibrils, along with the absence of amyloid fibers in the AFM and transmission electron microscopy images, suggest that medin aggregation into pores follows a nonamyloidogenic pathway. In silico modeling by mol. dynamics simulations provides at.-level structural detail of medin pores with the CNpNC barrel topol. and diameters comparable to values estimated from exptl. pore conductances. This study involved multiple reactions and reactants, such as (2R,9Z)-1-(((2-Aminoethoxy)(hydroxy)phosphoryl)oxy)-3-(palmitoyloxy)propan-2-yl oleate (cas: 26662-94-2Synthetic Route of C39H76NO8P).
(2R,9Z)-1-(((2-Aminoethoxy)(hydroxy)phosphoryl)oxy)-3-(palmitoyloxy)propan-2-yl oleate (cas: 26662-94-2) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Synthetic Route of C39H76NO8P
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics