Inhibition of glucosidase

N. Panday, Y. Canac, and A. Vasella, Very strong inhibition of glucosidases by C(2)-substituted tetrahydroimidazopyridines, Helv. Chim. Acta, 83 (2000) 58—79. 

Another common mechanism of correction is ER glucosidase inhibition (Fig. 1, star 2), which prevents the recognition of misfolded proteins by calnexin and calreticulin and presumably allows them to escape the ERQC. Inhibition of glucosidase with castanospermine and miglustat were shown to correct the trafficking of deltaE508 CFTR and alpha-l-antitrypsin (51, 61). Whether this mechanism also works on other ER-retained mutants remains to be determined. 

Another derivative of conduritol B, 6-bromo-3,4,5-trihydroxycyclohex-1-ene (bromoconduritol), was found to be effective for covalent inhibition of glucosidases. It reacts rapidly with an a-glucosidase from yeast (maltase) at equimolar concentrations of enzyme and inhibitor. It also reacts with )3-glucosidases from Cicer arietum and Alocasia maxrorrhiza. ... 

Inhibition of Glucosidases with Bromoconduritol. a-Glucosidase from yeasf and /8-glucosidases from Cicer arietum and Alocasia macrorrhiza show a time-dependent, irreversible inhibition with very low concentrations of bromoconduritol. Prom experiments with preparations partially enriched with respect to A or B, it was found that isomer A reacts with a-glucosidase whereas the above 8-glucosidases react preferentially with B. 

Bromoadenosine monophosphate, 99 3-Bromo-2-butanone-l,4-diol diethyl ketal, synthesis of, 393, 394 Bromocolchicine, 567-571 binding to brain extracts, 570,571 synthesis of, 569 Bromoconduritol, 369,370 inhibition of glucosidase, 381 synthesis of, 380, 381 a-Bromo-ft>-(3-cyanophenyl)alkane, 122 6-Bromo-6-deo conduritol B epoxide, active site labeling, 377-380 3-Bromo-l,4-dihydroxy-2-butanone 1,4-bisphosphate, 142, 392, 396, 397 synthesis of, 392-395... 

The first member of this class, acarbose, was introduced in the early 1990s. a-Glucosidase inhibitors slow the intestinal process of carbohydrate digestion by competitive inhibition of the activity of a-glucosidase enzymes located in the brush border of the enterocytes... 

Acarbose and Miglitol These agents are specific inhibitors of intestinal glucosidases and reduce the conversion of sucrose and starch to glucose. Their main effect is a delay, not a complete inhibition, of the absorption of carbohydrates. Postprandial blood sugar excursions are effectively reduced. Because a small portion of the carbohydrates enters the colon, their microbial degradation frequently causes flatulence or... 

Inhibition of o-Glucosidase Aj from Aspergillus wentii and / D-Gluco idase B (Ref. 51) from Bitter Almonds by Basic and Non-Basic Derivatives of D-Glucose... 

Fig. 3.—pH-Dependenceofthe Inhibition of -o-Glucosidase A, from Aspergillus wentiiby )3-D-Glucosylpyridinium Ion, left ordinate) and the Protonated Form of D-Glucosyl-amine right, calc, with pK, 5.6) and Nojirimycin (—A-, right, calc, with pK,... 

Inhibition of D-Mannosidases and D-Glucosidases by Swainsonine and Castanospermine, Respectively... 

Castanospermine is a plant alkaloid isolated from the seeds of the Australian chestnut tree, Castanospermium australe. As with most anti-HIV inhibitors, the discovery of the compound predates the time of isolation of HIV-1. The compound inhibits a-glucosidase-1, and therefore normal processing of the glycopro-... 

Saul R, Molyneux RJ, Elbein AD. (1984) Studies on the mechanism of castano-spermine inhibition of a- and 13-glucosidase. Arch Biochem Biophys2M 668-675. 

Fleet GWJ, Nicholas SJ, Smith PW, Evans SV, Fellows LE, Nash RJ. (1985) Potent competitive inhibition of a-galactosidase and a-glucosidase activity by l,4-dideoxy-l,4-iminopentitols Synthesis of l,4-dideoxy-l,4-imino-D-lyxitol and of both enantiomers of l,4-dideoxy-l,4-iminoarabinitol. 

Acid glucan-Lq-a-glucosidase (mouse) Inhibition of enzyme activity by 0.3 mM HA with parallel inhibition of glucose-stimulated insulin release 58... 

Table II. Inhibition of Natural B-Glucosidase Activity by Addition of Similar Glucosidases...

Figure 5. Tannin inhibition of Helicxmius 0-glucosidases that interfere with cyanogenesis of Passiflora.

The year 1979 was also the year of the first true breakthrough of the imino sugars. This was initiated by a medical researcher with Bayer company, Dr. W. Puls, who suggested a novel therapeutic concept for the treatment of diabetes type 2 symptoms after carbohydrate uptake this involved the inhibition of intestinal a-glucosidases with various compounds found in fermentation broths, among them 1,5-dideoxy-... 

In contrast to the inactive parent compound 2, inhibition of glycoprotein-processing oc-glucosidases was also found by Butters and coworkers for 1-deoxynojirimycin derivatives having phenylalkyl substituents of medium chain lengths (C4—C6) at the ring nitrogen atom.359... 

I. Miwa, J. Okuda, T. Horie, and M. Nakayama, Inhibition of intestinal a-glucosidases and sugar absorbtion by flavones, Chem. Pharm. Bull., 34 (1986) 838-844. 

M. L. Shulman, S. D. Shiyan, and A. Y. Khorlin, Specific irreversible inhibition of sweet-almond p-glucosidase by some p-glycopyranosylepoxyalkanes and p-D-glucopyranosyl isothiocyanate, Biochim. Biophys. Acta, 445 (1976) 169—181. 

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