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This post was written during early stages of trying to understand a complex scientific problem, and we didn't get everything right. The original author no longer endorses the content of this post. It is being left online for historical reasons, but read at your own risk.
Chaperone protein (from Wikipedia):
New functions for chaperones continue to be discovered, such as assistance in protein degradation, bacterial adhesin activity, and in responding to diseases linked to protein aggregation (e.g. see prion).
“Preventing misfolding of the prion protein by trimethylamine N-oxide,” Bennion et al., Biochemistry (2004)
Transmissible spongiform encephalopathies are a class of fatal neurodegenerative diseases linked to the prion protein. The prion protein normally exists in a soluble, globular state (PrP(C)) that appears to participate in copper metabolism in the central nervous system and/or signal transduction. Infection or disease occurs when an alternatively folded form of the prion protein (PrP(Sc)) converts soluble and predominantly alpha-helical PrP(C) into aggregates rich in beta-structure. The structurally disordered N-terminus adopts beta-structure upon conversion to PrP(Sc) at low pH. Chemical chaperones, such as trimethylamine N-oxide (TMAO), can prevent formation of PrP(Sc) in scrapie-infected mouse neuroblastoma cells [Tatzelt, J., et al. (1996) EMBO J. 15, 6363-6373]. To explore the mechanism of TMAO protection of PrP(C) at the atomic level, molecular dynamics simulations were performed under conditions normally leading to conversion (low pH) with and without 1 M TMAO. In PrP(C) simulations at low pH, the helix content drops and the N-terminus is brought into the small native beta-sheet, yielding a PrP(Sc)-like state. Addition of 1 M TMAO leads to a decreased radius of gyration, a greater number of protein-protein hydrogen bonds, and a greater number of tertiary contacts due to the N-terminus forming an Omega-loop and packing against the structured core of the protein, not due to an increase in the level of extended structure as with the PrP(C) to PrP(Sc) simulation. In simulations beginning with the “PrP(Sc)-like” structure (derived from PrP(C) simulated at low pH in pure water) in 1 M TMAO, similar structural reorganization at the N-terminus occurred, disrupting the extended sheet. The mechanism of protection by TMAO appears to be exclusionary in nature, consistent with previous theoretical and experimental studies. The TMAO-induced N-terminal conformational change prevents residues that are important in the conversion of PrP(C) to PrP(Sc) from assuming extended sheet structure at low pH.
“Doxycycline and protein folding agents rescue the abnormal phenotype of familial CJD H187R in a cell model,” Gu, Singh, Molecular Brain Research 123 (2004) 37-44
Similarly, chemical chaperones like glycerol and DMSO have been shown to assist protein refolding and prevent PrP(Sc) propagation in cell models [2,29]. Although quinacrine is also known to prevent PrP(Sc) replication, it shows a paradoxical effect on PrP(187-GFP) transport. Instead of facilitating transport, it causes increased accumulation of PrP(187-GFP) in the lysosomes. The differential effect of this durg on PrP(Sc) and PrP(187-GFP) is probably due to the difference in subcellular compartments where infectious and mutant PrP misfold. Doxycycline, on the other hand, restores normal transport of PrP(187R) in 80% of the cells at concentrations comparable to plasma levels following an oral dose of 250-600 mg two to three times daily . Since Doxycycline is a safe drug that is already in use in the human population, further investigations into its use are warranted to fully ascertain its promise as a preventative or therapeutic drug for CJD H187R and other familial prion disorders that share similar etiology.
 C.R. Brown, L.Q. Hong-Brown, J. Biwersi, A.S. Verkman, W.J. Welch, Chemical Chaperones correct the mutant phenotype of the delta F508 cystic fibrosis transmembrane conductance regulator protein, Cell Stress Chaperones (1996) 117-125.
 J. Tatzelt, S.B. Prusiner, W.J. Wlch, Chemical chaperones interfere with the formation of scrapie prion protein, EMBO J. 15 (1996) 6363-6373
“Prion proteins” by Byron Caughey, (2001) page 248
In contrast to “classical” chaperones consisting of proteins, chemical chaperones represent chemical compounds of small molecular weight that are able to stabilize proteins and correct misfolded ones (Welch and Brown, 1996.) Chemical chaperones such as glycerol, trimethylamine-N-oxide (TMAO), and dimethyl sulfoxide (DMSO) might stabilize the native conformation of a protein by direct interaction. These compounds termed “cellular osmolytes” are produced in cells in response to osmotic shock (Somero, 1986). Glycerol, TMAO and DMSO were tested to determine their influence of the formation of PrP(Sc) in ScN2a cells (Tatzelt et al., 1996b). All reduced the extent of PrP converstion to its detergent insoluble form. The stabilizing effect of the native form of a protein was also demonstrated for other proteins such as the cystic fibrosis transmembrane regulator (CFTR) (Brown et al, 1996). The presence of chemical chaperones might have an effect on the hydration of proteins. Because self-association or tighter packaging of the prion protein is enhanced, PrP(Sc) fails to interact with PrP(c) so that no PrP(c)/PrP(Sc) heterodimer is formed leading to an inhibition of the PrP conversion process (Gekko and Timasheff, 1981). In the case that chemical chaperones might be transported to the brain bypassing the blood-brain barrier (BBB), they might be useful as therapeutic agents in TSE-therapy.
“Chemical chaperone and inhibitor discovery: potential treatments for prion conformational diseases<’ Zhao et al., Perspecitives in Medicinal Chemistry (2007) 39-48
An increasing number of studies have indicated that some low-molecular-weight compounds named as chemical chaperones can reverse the mislocalization and/or aggregation of proteins associated with human conformational diseases. These small molecules are thought to non-selectively stabilize proteins and facilitate their folding. In this review, we summarize the probable mechanisms of protein conformational diseases in humans and the use of chemical chaperones and inhibitors as potential therapeutic agents against these diseases. Furthermore, recent advanced experimental and theoretical approaches underlying the detailed mechanisms of protein conformational changes and current structure-based drug designs towards protein conformational diseases are also discussed. It is believed that a better understanding of the mechanisms of conformational changes as well as the biological functions of these proteins will lead to the development and design of potential interfering compounds against amyloid formation associated with protein conformational diseases.