Linked Life Data

20347317

Source:http://linkedlifedata.com/resource/pubmed/id/20347317

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-4-12
pubmed:abstractText
Elevated levels of activated Protein Kinase B (PKB/Akt) have been detected in many types of human cancer. In contrast to ATP site inhibitors, substrate-based inhibitors are more likely to be selective because of extensive interactions with the specific substrate binding site. Unfortunately, peptide-based inhibitors lack important pharmacological properties that are required of drug candidates. Chemical modifications of potent peptide inhibitors, such as peptoids and N(alpha)-methylated amino acids, may overcome these drawbacks, while maintaining potency. We present a structure-activity relationship study of a potent, peptide-based PKB/Akt inhibitor, PTR6154. The study was designed to evaluate backbone modifications on the inhibitory activity of PTR6154. Two peptidomimetic libraries, peptoid and N(alpha)-methylation, based on PTR6154, were synthesized and evaluated for in vitro PKB/Akt inhibition efficiency. All the peptoid analogs reduced potency significantly, as well as most of the members of the N-methyl library, suggesting that the backbone conformation and/or hydrogen bond interactions of PTR6154 derivatives are essential for inhibition activity. Two N-terminal members of the N-methyl library did not decrease potency and can be used as future drug leads.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1464-3391
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2976-85
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Synthesis and structure-activity relationship studies of peptidomimetic PKB/Akt inhibitors: the significance of backbone interactions.
pubmed:affiliation
Institute of Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't