Description
Historically isolated from Kitasatosporia kifunense.1?Kifunensine (CAS 109944-15-2) is an inhibitor of class I α-mannosidases which inhibit glycoprotein processing. Inhibits human endoplasmic reticulum α-1,2-mannosidase I and Golgi Class I mannosidases IA, IB and IC with Ki values of 130 and 23 nM respectively.2 Inhibition of endoplasmic reticulum a-mannosidase I activity rescues the human a-sarcoglycan R77C mutation suggesting a new pharmacological approach for limb girdle muscular dystrophy type 2D patients carrying mutations that impair a-sarcoglycan trafficking.3 Improves maturation of misfolded proteins.4
Chemical Properties
White Powder
Uses
Kifunensine is an alkaloid produced by the fungus, Kitasatosporia kifunense, and has been shown to be a weak inhibitor of aryl mannosidase. It is a unique oxamide derivative of mannojirimycin and a potent inhibitor of the glycoprotein processing enzyme mannosidase I. Kifunenesine is ineffective in inhibiting either mannosidase II or the endoplasmic reticulum (ER) a-mannosidase. It also possesses immunomodulating properties based on chemical, physicochemical and x-ray crystallographic analysis.When tested in cell culture using influenza virus-infected MDCK cells, kifunensine, at 1 mg/ml or less, caused almost complete inhibition of complex chain formation with the accumulation of Man9(GlcNAc)2. Thus, kifunensine was proven to be 50 to 100 times more effective than deoxymannojirimycin.Ph
General Description
A potent alkaloid inhibitor of mannosidase I. Does not affect mannosidase II and the endoplasmic reticulum α-mannosidase.
Biological Activity
Inhibitor of class I α -mannosidases that inhibits glycoprotein processing. Inhibits human endoplasmic reticulum α -1,2-mannosidase I and Golgi Class I mannosidases IA, IB and IC with K i values of 130 and 23 nM respectively.
Biochem/physiol Actions
Product does not compete with ATP.
References
1)?Iwami et al. (1987), A new immunomodulator, FR-900494: taxonomy, fermentation, isolation, and physico-chemical and biological characteristics; J.Antibiot. (Tokyo) 40 612
2)?Elbein et al. (1990), Kifunensine, a potent inhibitor of the glycoprotein processing mannosidase I; ?J.Biol.Chem. 265 15599
3)?Bartoli et al. (2008), Mannosidase I inhibition rescues the human alpha-sarcoglycan R77C recurrent mutation; ?Hum.Mol.Genet. 17 1214
4)?Wang et al. (2011), Inhibition of endoplasmic reticulum-associated degradation rescues native folding in loss of function protein misfolding diseases; J.Biol.Chem. 286 43454
