Craig Webster <Craig at broombio.demon.co.uk> wrote:
>In article: <496ti5$bk0 at dux.dundee.ac.uk> (k.c.breen at dundee.ac.uk) writes:
>>>> I was wondering if there are any commercially available inhibitors of
>> terminal glycosyltransferases (specifically sialyltransferase and
>> galactosyltransferase). In particular, I am interested in agents
>> which can be used to treat cells in order to subtly alter their
>> protein glycosylation patterns. I have tried mannosidase inhibitors,
>> but these act at an early stage in oligosaccharide elongation and
>> processing to prevent the transfer of a number of terminal
>> sugar residues
>>>Would Tunicamycin be of any use in this case ?
I think tunicamycin would halt addition of N-glycans full stop!! - since
it is an inhibitor of the first GlcNAc transferase in formation of the
dolichyl-linked oligosaccharide precursor. However, in answer to Dr.
Breen's original question - I don't personally know of any commercially
available cell-culture suitable reagents of the kind he requires (I am
open to correction on this). Field, R.A., et al at Dundee
Chemistry/Biochemistry departments do have a paper in Bio-organic and
Medicinal Chemistry Letters (1994, vol. 4, pp. 391-394) on inhibitors of
galactosyltransferase - but the inhibitor found was only tested in vitro
(for the paper). Another approach - more sophisticated/expensive is to
use antisense oligodeoxynucleotides - I'm not joking - this approach has
been reported to be successful with GM2 and GD3 synthase (ganglioside
glycosyltransferases) - see Zeng et al in Proc. Natl. Acad. Sci. USA
(1995, vol. 92, pp. 8670-8674).
Iain
--
Iain Wilson Institut fuer Chemie
Tel: 43-1-47654-6065 Universitaet fuer Bodenkultur
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