Linked Life Data

10479306

Source:http://linkedlifedata.com/resource/pubmed/id/10479306

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1999-10-14
pubmed:abstractText
A series of small peptides with the sequence mAZ-pTyr-Xaa-Asn-NH(2), where Xaa denotes alpha-methylphosphotyrosine or its carboxylic mimetics, were synthesized as inhibitors of the Grb2 SH2 domain. Peptide 3 with (alpha-Me)pTyr as Xaa has the highest affinity for Grb2 (K(d) = 3 +/- 1 nM) and exhibits to date the best inhibitory activity (IC(50) = 11 +/- 1 nM) to displace PSpYVNVQN-Grb2 interaction in an ELISA test. The lower affinities of peptides with (alpha-Me)Tyr, (alpha-Me)Phe(4-CO(2)H), or (alpha-Me)Phe(4-CH(2)CO(2)H) as Xaa demonstrate the importance of a double charged phosphate group at the pY+1 position. Molecular modeling showed additional hydrogen bond interactions provided by the (alpha-Me)pTyr residue with the Grb2 SH2 domain. These results thus show that the effect of hydrophobic pY+1 residues, initially put forth to increased the binding affinities, can be further enhanced by a (-Me)pTyr residue which has both hydrophobic and hydrophilic properties.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3737-41
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Small peptides containing phosphotyrosine and adjacent alphaMe-phosphotyrosine or its mimetics as highly potent inhibitors of Grb2 SH2 domain.
pubmed:affiliation
Département de Pharmacochimie Moléculaire et Structurale, INSERM U266-CNRS UMR 8600, UFR des Sciences Pharmaceutiques et Biologiques, 4, avenue de l'Observatoire, 75270 Paris Cedex 06, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't