Linked Life Data

7880809

Source:http://linkedlifedata.com/resource/pubmed/id/7880809

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1995-4-13
pubmed:abstractText
Neuraminidase (NA), a surface glycoprotein of influenza virus, is a potential target for design of antiinfluenza agents. The crystal structure of influenza virus neuraminidase showed that in the active site 11 residues are universally conserved among all strains known so far. Several potent inhibitors based on the carbohydrate compound 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (DANA) have been shown to bind to the conserved active site and to reduce virus infection in animals when administered by nasal spray. Inhibitors of this type are, however, rapidly excreted from physiological systems and may not be effective in order to provide long-time protection. A new class of specific NA inhibitors, which are benzoic acid derivatives, has been designed on the basis of the three-dimensional structure of the NA-DANA complex and modeling of derivatives of 4-(acetylamino)benzoic acid in the NA active site. Intermediates were synthesized and were shown to moderately inhibit the NA activity and to bind to the NA active site as predicted. These rudimentary inhibitors, 4-(acetylamino)-3-hydroxy-5-nitrobenzoic acid, 4-(acetylamino)-3-hydroxy-5-aminobenzoic acid, and 4-(acetylamino)-3-aminobenzoic acid, and their X-ray structures in complexes with N2 (A/Tokyo/3/67) and B/Lee/40 neuraminidases have been analyzed. The coordinates of such inhibitors complexed with NA were used as the starting model for further design of more potent benzoic acid inhibitors. Because the active site residues of NA are invariant, the designed aromatic inhibitors have the potential to become an antiviral drug against all strains of influenza virus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3144-51
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Structures of aromatic inhibitors of influenza virus neuraminidase.
pubmed:affiliation
Department of Microbiology, University of Alabama at Birmingham 35294.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.