Natural (and Unnatural) Small Molecules as Pharmacological Chaperones and Inhibitors in Cancer

2017 ◽  
pp. 155-190 ◽  
Author(s):  
Isabel Betancor-Fernández ◽  
David J. Timson ◽  
Eduardo Salido ◽  
Angel L. Pey
Keyword(s):  
Small Molecules ◽  
Pharmacological Chaperones

Screening methods for identifying pharmacological chaperones

2017 ◽  
Vol 13 (4) ◽  
pp. 638-647 ◽  
Author(s):  
Min Hyeon Shin ◽  
Hyun-Suk Lim
Keyword(s):  
Small Molecules ◽  
Misfolded Proteins ◽  
Screening Methods ◽  
Pharmacological Chaperones

This review highlights recent screening methods for identifying pharmacological chaperones, which are small-molecules capable of rescuing misfolded proteins.

scholarly journals Galactosemia: Towards Pharmacological Chaperones

2021 ◽  
Vol 11 (2) ◽  
pp. 106
Author(s):  
Samantha Banford ◽  
Thomas J. McCorvie ◽  
Angel L. Pey ◽  
David J. Timson
Keyword(s):  
Small Molecules ◽  
Enzyme Function ◽  
Current Therapy ◽  
Cognitive Disability ◽  
Novel Therapies ◽  
Biochemical Basis ◽  
Pharmacological Chaperones ◽  
Exciting Potential ◽  
Fundamental Cause ◽  
Life Threatening

Galactosemia is a rare inherited metabolic disease resulting from mutations in the four genes which encode enzymes involved in the metabolism of galactose. The current therapy, the removal of galactose from the diet, is inadequate. Consequently, many patients suffer lifelong physical and cognitive disability. The phenotype varies from almost asymptomatic to life-threatening disability. The fundamental biochemical cause of the disease is a decrease in enzymatic activity due to failure of the affected protein to fold and/or function correctly. Many novel therapies have been proposed for the treatment of galactosemia. Often, these are designed to treat the symptoms and not the fundamental cause. Pharmacological chaperones (PC) (small molecules which correct the folding of misfolded proteins) represent an exciting potential therapy for galactosemia. In theory, they would restore enzyme function, thus preventing downstream pathological consequences. In practice, no PCs have been identified for potential application in galactosemia. Here, we review the biochemical basis of the disease, identify opportunities for the application of PCs and describe how these might be discovered. We will conclude by considering some of the clinical issues which will affect the future use of PCs in the treatment of galactosemia.

scholarly journals Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations

2020 ◽  
Vol 21 (2) ◽  
pp. 489 ◽  
Author(s):  
Ludovica Liguori ◽  
Maria Monticelli ◽  
Mariateresa Allocca ◽  
Bruno Hay Mele ◽  
Jan Lukas ◽  
...  
Keyword(s):  
Small Molecules ◽  
Specific Binding ◽  
Total Activity ◽  
Missense Mutations ◽  
Lysosomal Storage ◽  
Pharmacological Chaperone ◽  
Mutant Proteins ◽  
Pharmacological Chaperones ◽  
Protein Mutants ◽  
Competitive Inhibitors

The term “pharmacological chaperone” was introduced 20 years ago. Since then the approach with this type of drug has been proposed for several diseases, lysosomal storage disorders representing the most popular targets. The hallmark of a pharmacological chaperone is its ability to bind a protein specifically and stabilize it. This property can be beneficial for curing diseases that are associated with protein mutants that are intrinsically active but unstable. The total activity of the affected proteins in the cell is lower than normal because they are cleared by the quality control system. Although most pharmacological chaperones are reversible competitive inhibitors or antagonists of their target proteins, the inhibitory activity is neither required nor desirable. This issue is well documented by specific examples among which those concerning Fabry disease. Direct specific binding is not the only mechanism by which small molecules can rescue mutant proteins in the cell. These drugs and the properly defined pharmacological chaperones can work together with different and possibly synergistic modes of action to revert a disease phenotype caused by an unstable protein.

Gap junctions in the prothoracic glands of the tobacco hornworm, Manduca sexta

1992 ◽  
Vol 50 (1) ◽  
pp. 706-707
Author(s):  
Ji-da Dai ◽  
M. Joseph Costello ◽  
Lawrence I. Gilbert
Keyword(s):  
Gap Junctions ◽  
Small Molecules ◽  
Manduca Sexta ◽  
Freeze Fracture ◽  
Cell Communication ◽  
Cellular Level ◽  
Thin Sections ◽  
Prothoracic Glands ◽  
Polyhydroxylated Steroids ◽  
Stimulation Of

Insect molting and metamorphosis are elicited by a class of polyhydroxylated steroids, ecdysteroids, that originate in the prothoracic glands (PGs). Prothoracicotropic hormone stimulation of steroidogenesis by the PGs at the cellular level involves both calcium and cAMP. Cell-to-cell communication mediated by gap junctions may play a key role in regulating signal transduction by controlling the transmission of small molecules and ions between adjacent cells. This is the first report of gap junctions in the PGs, the evidence obtained by means of SEM, thin sections and freeze-fracture replicas.

Fusion and Fission Processes in Exocytosis: Possible Roles for Synexin and Osmotic Lysis in the Two Events

1980 ◽  
Vol 38 ◽  
pp. 594-597
Author(s):  
H.B. Pollard ◽  
C.E. Creutz ◽  
C.J. Pazoles ◽  
J.H. Scott
Keyword(s):  
Small Molecules ◽  
Chromaffin Cells ◽  
Adrenal Glands ◽  
General Concept ◽  
Extracellular Calcium ◽  
Large Protein ◽  
Granule Membrane ◽  
Osmotic Lysis ◽  
Per Se ◽  
Chemical Evidence

Exocytosis is a general concept describing secretion of enzymes, hormones and transmitters that are otherwise sequestered in intracellular granules. Chemical evidence for this concept was first gathered from studies on chromaffin cells in perfused adrenal glands, in which it was found that granule contents, including both large protein and small molecules such as adrenaline and ATP, were released together while the granule membrane was retained in the cell. A number of exhaustive reviews of this early work have been published and are summarized in Reference 1. The critical experiments demonstrating the importance of extracellular calcium for exocytosis per se were also first performed in this system (2,3), further indicating the substantial service given by chromaffin cells to those interested in secretory phenomena over the years.

Effect of Alkyl Substituents on DPP‐based Small Molecules for Organic Solar Cells

2020 ◽  
Author(s):  
Seunggyun Hong ◽  
Eunhee Lim
Keyword(s):  
Solar Cells ◽  
Small Molecules ◽  
Organic Solar Cells

HIGH RESOLUTION SPECTROSCOPIC STUDIES OF SMALL MOLECULES

1987 ◽  
Vol 48 (C7) ◽  
pp. C7-17-C7-28 ◽  
Author(s):  
R. W. FIELD
Keyword(s):  
High Resolution ◽  
Small Molecules ◽  
Spectroscopic Studies

Innovative Radiotracer: Peptide und Small Molecules

2009 ◽  
Vol 181 (S 01) ◽  
Author(s):  
HJ Wester ◽  
I Dijkgraaf ◽  
M Schottelius ◽  
G Henriksen ◽  
M Schwaiger
Keyword(s):  
Small Molecules

Pollen induced asthma – could small molecules in pollen exacerbate the protein-mediated allergic response?

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
A Bozicevic ◽  
M De Mieri ◽  
C Nassenstein ◽  
M Hamburger
Keyword(s):  
Small Molecules ◽  
Allergic Response
Sign in / Sign up

Export Citation Format

Share Document