| Title |
The design of potential antidiabetic drugs: experimental investigation of a number of β-D-glucose analogue inhibitors of glycogen phosphorylase
|
|---|---|
| Published in |
European Journal of Drug Metabolism and Pharmacokinetics, September 1994
|
| DOI | 10.1007/bf03188920 |
| Pubmed ID | |
| Authors |
N. G. Oikonomakos, M. Kontou, S. E. Zographos, H. S. Tsitoura, L. N. Johnson, K. A. Watson, E. P. Mitchell, G. W. J. Fleet, J. C. Son, C. J. F. Bichard, D. D. Leonidas, K. R. Acharya |
| Abstract |
alpha-D-glucose is a weak inhibitor (Ki = 1.7 mM) of glycogen phosphorylase (GP) and acts as physiological regulator of hepatic glycogen metabolism; it binds to GP at the catalytic site and stabilizes the inactive T state of the enzyme promoting the action of protein phosphatase 1 and stimulating glycogen synthase. The three-dimensional structures of T state rabbit muscle GPb and the GPb-alpha-D-glucose complex have been exploited in the design of better regulators of GP that could shift the balance between glycogen synthesis and glycogen degradation in favour of the former. Close examination of the catalytic site with alpha-D-glucose bound shows that there is an empty pocket adjacent to the beta-1-C position. beta-D-glucose is a poorer inhibitor (Ki = 7.4 mM) than alpha-D-glucose, but mutarotation has prevented the binding of beta-D-glucose in T state GP crystals. A series of beta-D-glucose analogues has been designed and tested in kinetic and crystallographic experiments. Several compounds have been discovered that have an increased affinity for GP than the parent compound. |
Mendeley readers
The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 10 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Professor > Associate Professor | 2 | 20% |
| Student > Bachelor | 2 | 20% |
| Other | 1 | 10% |
| Researcher | 1 | 10% |
| Student > Master | 1 | 10% |
| Other | 0 | 0% |
| Unknown | 3 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 30% |
| Chemistry | 2 | 20% |
| Computer Science | 1 | 10% |
| Unknown | 4 | 40% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 July 2011.
All research outputs
#4,695,994
of 22,785,242 outputs
Outputs from European Journal of Drug Metabolism and Pharmacokinetics
#35
of 423 outputs
Outputs of similar age
#2,584
of 21,548 outputs
Outputs of similar age from European Journal of Drug Metabolism and Pharmacokinetics
#1
of 6 outputs
Altmetric has tracked 22,785,242 research outputs across all sources so far. Compared to these this one has done well and is in the 76th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 423 research outputs from this source. They receive a mean Attention Score of 3.4. This one has done well, scoring higher than 83% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 21,548 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them