Linked Life Data

17692431

Source:http://linkedlifedata.com/resource/pubmed/id/17692431

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-5-9
pubmed:abstractText
To study the structure-activity relationships (SAR) and the binding activity of pro-apoptotic Bak BH3 domain, we synthesised several 16mer peptide analogues corresponding to the region (72)-GQVGRQLAIIGDDINR-(87). Using different amino acids varying in length, steric and electronic properties, we investigated the role and the nature of physicochemical parameters of residues Val74, Leu78, Ile81 and Ile85, previously identified to be crucial for interactions. With this aim, we measured the affinity of these peptides on two anti-apoptotic proteins Bcl-x(L) and Bcl-2 by a polarization fluorescence competitive assay. We defined that the most potent peptide on Bcl-x(L), which presents a 4.6-fold increase as compared to the parent peptide affinity, was obtained when Ile85 was mutated with a 4-chlorophenylalanine. Finally, assays of eight Bak peptide analogues on Bcl-2 allowed us to postulate that modulations at position 78 could afford peptides with a binding selectivity enhanced for Bcl-x(L). These pharmacological and physicochemical parameter data should prove useful for the rational design of non-peptide ligands as potential antagonists of Bcl-2 protein interactions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0223-5234
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
966-72
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Structure-activity relationships of Bak derived peptides: affinity and specificity modulations by amino acid replacement.
pubmed:affiliation
INSERM, U554, Montpellier, F-34090, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't