Linked Life Data

18290604

Source:http://linkedlifedata.com/resource/pubmed/id/18290604

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-3-21
pubmed:abstractText
A new class of inhibitors 4-oxo-beta-lactams (azetidine-2,4-diones), containing the required structural elements for molecular recognition, inhibit porcine pancreatic elastase (PPE) but show a dramatically lower reactivity toward hydroxide compared with the analogous inhibitors 3-oxo-beta-sultams. Inhibition is the result of acylation of the active site serine and electron-withdrawing substituents at the N-(4-aryl) position in 3,3-diethyl- N-aryl derivatives increasing the rate of enzyme acylation and generating a Hammett rho-value of 0.65. Compared with a rho-value of 0.96 for the rates of alkaline hydrolysis of the same series, this is indicative of an earlier transition state for the enzyme-catalyzed reaction. Docking studies indicate favorable noncovalent interactions of the inhibitor with the enzyme. Compound 2i, the most potent inhibitor against PPE, emerged as a very potent HLE inhibitor, with a second-order rate for enzyme inactivation of approximately 5 x 10 (5) M (-1) s (-1).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1783-90
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Azetidine-2,4-diones (4-oxo-beta-lactams) as scaffolds for designing elastase inhibitors.
pubmed:affiliation
iMed UL, CECF, Faculdade de Farmácia, Universidade de Lisboa, Av. Forças Armadas, Lisbon, Portugal.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't