Designation of imidazole-containing dipeptides as pharmacological chaperones.

Abstract

We review the dichotomous regulatory roles of natural imidazole-containing peptidomimetics (N-acetylcarnosine [NAC], carcinine, non-hydrolized carnosine) in maintaining skin homeostasis that determines whether keratinocytes survive or undergo apoptosis in response to various insults and in the development of skin diseases. General strategies addressing common ground techniques to improve absorption of usually active chaperone proteins or their dipeptide inducer (usually poorly absorbed) compounds include encapsulation into hydrophobic carriers, combination with penetration enhancers, active electrical transport or chemical modification to increase hydrophobicity. A growing evidence is presented that demonstrates the ability of NAC (lubricant eye drops) or carcinine to act as pharmacological chaperones, or being synergistically coupled in patented formulations with another imidazole-containing peptidomimetic (such as, Leucyl-histidylhydrazide), to decrease oxidative stress and ameliorate oxidative and excessive glycation stress-related eye disease phenotypes, suggesting that the field of chaperone therapy might hold novel treatments for age-related cataracts, glaucoma, age-related macular degeneration (AMD), and ocular complications of diabetes (OCD). Current efforts are being directed towards exploring therapeutic approaches of pharmacological targeting and human drug delivery for chaperone molecules based on innovative patented strategies.

• Authors: Mark A Babizhayev
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 30 Issue 7 Pg. 736-61 (Jul 2011) ISSN: 1477-0903 [Electronic] England
• PMID: 20656726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Drug Carriers
• Imidazoles
• Molecular Chaperones
• N-acetylcarnosine
• imidazole
• Carnosine
• carcinine

Topics

• Carnosine (analogs & derivatives, chemistry, therapeutic use)
• Cataract (drug therapy, metabolism)
• Drug Carriers
• Humans
• Imidazoles (chemistry, therapeutic use)
• Lipid Peroxidation (drug effects)
• Macular Degeneration (drug therapy, metabolism)
• Molecular Chaperones
• Oxidative Stress (drug effects)