Question

What is osmolytes? What is the molecule and its positive effect on protein refolding? What are similar molecules that are being investigated as curative agents?

Answer 1

Osmolytes are organic compounds of low molecular weight which influence the biological fluid properties.When a cell swells due to external osmotic pressure, membrane channels open and allow efflux of osmolytes carrying water to restore normal cell volume. Osmolytes also interact with cell constituents, e.g. they influence protein folding.Amino acids, sugars and polyols, methylamines, methylsulfonium compounds and urea are common osmolytes.

Osmolytes provide protein stability via osmophobicity, preferential exclusion from protein surfaces, surface tension and volume exclusion. Those forces are responsible for a protein's stability.The properties of the osmolytes are assumed to compel the proteins to fold into a native conformation given the unwanted impact of adverse environmental conditions Based on the free energy transmission of the amino acid side chain and peptide backbone from water to osmolyte solution, the ability of osmolyte to stabilize protein is thought to evolve from the adverse interactions between osmolytes and the functional group, i.e. peptide backbone.To be aware of the influences of high pressure on biochemical systems, essential knowledge about the effects of pressure on the thermodynamic properties of such osmolytes is significant. The study showed the high pressure effects on various biochemical systems where a specific focus was placed on the effects of pressure on osmolytes such as TMAO,Acetyl-N-methylglycine amide, acetyl-N-methylalanine amide, acetyl-N-methylalanine amide, and acetyl-N-methyl leucine amide.The study also reported the ability of osmolytes such as polyethylene glycol and TMAO to inhibit the depolymerization of individual microtubule filaments and could potentially play an essential role in the dynamics of in vivo microtubules.

Most neurological disorders in the brain are caused by misfolded or aggregated proteins buildup abnormal.These molecules help to provide stability to the aggregated proteins and protect these proteins from misfolding. Alzheimer's disease (AD) is the ultimate universal neurological disorder that can be described by the deposition of amyloidβ-protein (Aβ) aggregated / misfolded protein.Osmolytes provide stability to a protein's folded, functional form, and change the folding balance away from protein aggregation and/or degradation. They're also identified as chemical chaperones. Brain osmolytes increase the rate of Aβaggregation, combine more easily with nearby water molecules, and prevent protein aggregation / misfolding by supplying them with stability.Thus, osmolytes can be used as therapeutic targets for many neurodegenerative and other diseases and may assist in potential drug design.

eg-Glysine,Choline Containing compound, Taurine, GABA, N-acetyl Aspartate, Betain, Ser,Gly,Ala, etc