| |
 |
|
|
Science Forum Index » Medicine - Nursing Forum » Caffeine Theophylline and Pentoxifylline...
Page 1 of 1
|
| Author |
Message |
| ironjustice at (no spam) aol.com... |
 Posted: Mon Jul 21, 2008 6:22 am |
|
|
|
Guest
|
Crystallographers widen therapeutic options for asthma
29 September 2005
Chemists have used crystallographic analysis to identify a group of
molecules they say could provide novel asthma drugs.
X-ray crystallographer Daan van Aalten at the University of Dundee, UK
and colleagues screened a library of marketed drug molecules looking
for inhibitors of an enzyme recently linked to asthma pathogenesis.
The discovery of the enzyme, chitinase, at high concentration in the
lungs of asthmatics surprised researchers last year. The enzyme breaks
down chitin, a polymer of b(1,4)-linked N-acetlyglucosamine, which is
not found in humans but rather in numerous potential pathogens,
including insects, nematodes and fungi.
The group that made that discovery, led by Jack Elias, professor of
medicine at Yale University, US, suggested that chitinase would help
fight off infection by chitin-containing pathogens. In the absence of
such pathogens, the redundant enzyme might push the immune system
towards generating allergic reactions and asthma.
van Aaltan's group in Dundee screened a commercially available library
of 880 drug molecules against a fungal chitinase from Aspergillus
fumigatus. They found three chitinase inhibitors: theophylline and
pentoxifylline (two methylxanthine derivatives, which contain a common
1,3-dimethylxanthine substructure) and the closely related
methylxanthine, caffeine. Pentoxifylline was the most potent
inhibitor.
Crystallographic analysis of chitinase-inhibitor complexes revealed
specific interactions with the active site, said van Aalten.
Subsequent mutagenesis identified key active site residues related to
inhibitor affinity, he noted, and these sites are conserved in
mammalian chitinases.
The three methylxanthines offer great pharmacological promise, he
concluded. 'These molecules.provide attractive, synthetically
accessible scaffolds for further optimisation.' Bea Perks
ReferencesF V Rao et al, Chemistry & Biology, 2005, 12, 973
Z Zhu et al, Science, 2004, 304, 1678
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk |
|
|
| Back to top |
|
| |
|
Page 1 of 1
All times are GMT - 5 Hours
The time now is Sat Sep 06, 2008 11:07 am
|
|