Linked Life Data

11784133

Source:http://linkedlifedata.com/resource/pubmed/id/11784133

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-10
pubmed:abstractText
A novel class of tight binding carbonic anhydrase (CA) activators was designed by using histamine and histidine as lead molecules. Carnosine (beta-Ala-His) derivatives were synthesized by reaction of appropriately derivatized beta-alanines with imidazole/carboxy-protected histidine in the presence of carbodiimides, followed by removal of the various protecting groups. The derivatized beta-alanines mentioned above were in turn obtained by coupling of 4-fluorophenylsulfonylureido amino acids (fpu-AA) or 2-toluenesulfonylureido amino acids (ots-AA) with beta-Ala. Some structurally related dipeptides with the general formula fpu/ots-AA1-AA2 (AA, AA1, and AA2 represent amino acyl moieties) were also prepared by a similar strategy and used thereafter for obtaining CA activators incorporating a modified tetrapeptide scaffold. Many of the new tri-/tetrapeptide derivatives reported here proved to be efficient in vitro activators of three CA isozymes. Very good activity was detected against hCA I and bCA IV, for which some of the new compounds showed affinities in the 1-20 nM range (h = human; b = bovine isozymes), whereas against hCA II, their affinities were in the range of 10-40 nM. Ex vivo experiments showed some of the new activators to strongly enhance cytosolic red cell CA activity after incubation with human erythrocytes. This new class of CA activators might lead to the development of drugs/diagnostic tools for the management of CA deficiency syndromes, as well as for the pharmacological enhancement of synaptic efficacy, spatial learning, and memory. This may constitute a new approach for the treatment of Alzheimer's disease and other conditions in need of achieving memory therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
284-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Carbonic anhydrase activators: high affinity isozymes I, II, and IV activators, incorporating a beta-alanyl-histidine scaffold.
pubmed:affiliation
Università degli Studi, Laboratorio di Chimica Inorganica e Bioinorganica, Via Gino Capponi 7, I-50121 Florence, Italy.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't