PMID- 7929454
OWN - NLM
STAT- MEDLINE
DCOM- 19941123
LR  - 20210212
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 43
DP  - 1994 Oct 28
TI  - N-butyldeoxygalactonojirimycin inhibits glycolipid biosynthesis but does not 
      affect N-linked oligosaccharide processing.
PG  - 27108-14
AB  - We have previously reported that the imino sugar N-butyldeoxynojirimycin (NB-DNJ) 
      inhibits glycolipid biosynthesis, in addition to its known activity as an 
      inhibitor of the N-linked oligosaccharide processing enzyme alpha-glucosidase I. 
      In an attempt to dissociate these two activities and identify an inhibitor which 
      was more selective for the glycolipid biosynthetic pathway, several imino sugars 
      have been N-alkylated and tested for inhibitory activity. The galactose analogue 
      N-butyldeoxygalactonojirimycin (NB-DGJ) was found to be a potent inhibitor of 
      glycolipid biosynthesis but in contrast to NB-DNJ had no effect on the maturation 
      of N-linked oligosaccharides or on lysosomal glucocerebrosidase. The effect of 
      increasing N-alkyl chain length on glycolipid inhibition was investigated. 
      Nonalkylated DGJ, the N-methyl and N-ethyl derivatives, were noninhibitory. 
      However, N-propylation resulted in partial inhibition while the N-butyl and 
      N-hexyl derivatives resulted in maximal inhibition. Increasing alkyl chain length 
      also resulted in increased potency of glucosyltransferase inhibition. In an in 
      vitro Gaucher's disease model NB-DGJ was as effective as NB-DNJ in preventing 
      glycolipid storage and may represent a more selective potential therapeutic agent 
      than NB-DNJ for the management of this and other glycosphingolipidoses.
FAU - Platt, F M
AU  - Platt FM
AD  - Department of Biochemistry, University of Oxford, United Kingdom.
FAU - Neises, G R
AU  - Neises GR
FAU - Karlsson, G B
AU  - Karlsson GB
FAU - Dwek, R A
AU  - Dwek RA
FAU - Butters, T D
AU  - Butters TD
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Glycolipids)
RN  - 0 (Oligosaccharides)
RN  - 19130-96-2 (1-Deoxynojirimycin)
RN  - ADN3S497AZ (miglustat)
RN  - C4XNY919FW (migalastat)
RN  - EC 2.4.1.- (Glucosyltransferases)
RN  - EC 2.4.1.80 (ceramide glucosyltransferase)
RN  - EC 3.2.1.20 (alpha-Glucosidases)
RN  - EC 3.2.1.45 (Glucosylceramidase)
SB  - IM
MH  - 1-Deoxynojirimycin/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Gaucher Disease/metabolism
MH  - Glucosylceramidase/drug effects
MH  - Glucosyltransferases/antagonists & inhibitors
MH  - Glycolipids/*biosynthesis
MH  - Humans
MH  - Mice
MH  - Oligosaccharides/*biosynthesis
MH  - Structure-Activity Relationship
MH  - alpha-Glucosidases/drug effects
EDAT- 1994/10/28 00:00
MHDA- 1994/10/28 00:01
CRDT- 1994/10/28 00:00
PHST- 1994/10/28 00:00 [pubmed]
PHST- 1994/10/28 00:01 [medline]
PHST- 1994/10/28 00:00 [entrez]
AID - S0021-9258(18)47132-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Oct 28;269(43):27108-14.