Login

Journal Image
Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
VOLUME: 18
ISSUE: 1
DOI: 10.2174/092986711793979698









Chemical and Pharmacological Chaperones: Application for Recombinant Protein Production and Protein Folding Diseases

img
Author(s): Rahul S. Rajan, Kouhei Tsumoto, Masao Tokunaga, Hiroko Tokunaga, Yoshiko Kita and Tsutomu Arakawa
Pages 1-15 (15)
Abstract:
Since protein function depends on folding, successful development of active pharmaceutical proteins requires in vitro production of functional, properly folded proteins. In vitro protein folding and hence production can be assisted by co-solvents, including osmolytes and arginine. Osmolytes accumulate in the cytoplasm to raise the osmotic pressure against environmental water stresses, resulting in stabilization of proteins. They have shown to enhance in vitro and in vivo protein folding and suppress in vivo protein aggregation, thus called “chemical chaperones”. Requirement of high concentrations, however, eliminates possible applications of chemical chaperones to rescue in vivo misfolded proteins that cause various diseases. More specific ligands can serve a similar function at much lower concentrations and are called “pharmacological chaperones”. We will review here the applications of chemical chaperones for biotechnology product development and of pharmacological chaperones for in vivo protein folding, and the mechanism of their effects on protein folding. A specific case we review here is the mechanism of action of the polar amino acid arginine, which has been widely used in vitro as a chemical chaperone to assist protein folding and suppress aggregation.
Keywords:
Chemical chaperone, pharmacological chaperon, osmolyte, recombinant protein, halophile, Protein, biopharmaceutical development, pharmaceutical drugs, Osmolytes, polar natural, cytoplasm, cells, halophilic organisms, thermodynamic, compatible solutes, chaperones, Escherichia coli, insoluble proteins, inclusion bodies, solubility, Anifinsen's principle, hydrophobic, ionic, aggregate formation, dilution, dialysis, non-osmolyte arginine, protein solution, solvent, thermodynamic stability, antibodies, E. coli, solubilization, Sarcosine, glycerol, kinetics, lysozyme, mutants, Proline, severe acute syndrome (SARS), HETEROLOGOUS, Periplasmic Expression, Cytoplasmic Soluble Expression, enzymes, osmotic pressure, halophilic bacteria, green fluorescent protein (GFP), column chromatography, racemization activities, cystic fibrosis, pulmonary tissues, biogenesis, phenylalanine, glycosylation, proteasomal degradation, ribosome, Immunofluorescence, antitrypsin, phenyl butyric acid (PBA), nephrogenic diabetes, urine, vasopressin V2, hydration, equilibrium, globular proteins, high affinity, cell membranes
Affiliation:
Alliance Protein Laboratories, 3957 Corte Cancion, Thousand Oaks, CA 91360, USA.