Linked Life Data

19861237

Source:http://linkedlifedata.com/resource/pubmed/id/19861237

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2009-11-9
pubmed:abstractText
Sirtuins are NAD(+) dependent deacetylases that modulate various essential cellular functions. Development of peptide based inhibitors of Sir2s would prove useful both as pharmaceutical agents and as effectors by which downstream cellular alterations can be monitored. Click chemistry that utilizes Huisgen's 1,3-dipolar cycloaddition permits attachment of novel modifications onto the side chain of lysine. Herein, we report the synthesis of peptide analogues prepared using click reactions on Nepsilon-propargyloxycarbonyl protected lysine residues and their characterization as inhibitors of Plasmodiumfalciparum Sir2 activity. The peptide based inhibitors exhibited parabolic competitive inhibition with respect to acetylated-peptide substrate and parabolic non-competitive inhibition with NAD(+) supporting the formation of EI(2) and E.NAD(+).I(2) complexes. Cross-competition inhibition analysis with the non-competitive inhibitor nicotinamide (NAM) ruled out the possibility of the NAM-binding site being the second inhibitor binding site, suggesting the presence of a unique alternate pocket accommodating the inhibitor. One of these compounds was also found to be a potent inhibitor of the intraerythrocytic growth of P.falciparum with 50% inhibitory concentration in the micromolar range.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1464-3391
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8060-72
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Development and characterization of lysine based tripeptide analogues as inhibitors of Sir2 activity.
pubmed:affiliation
Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't