Linked Life Data

21650457

Source:http://linkedlifedata.com/resource/pubmed/id/21650457

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2011-7-21
pubmed:abstractText
Elevated levels of activated protein kinase B (PKB/Akt) have been detected in many types of cancer. Substrate-based peptide inhibitors have the advantage of selectivity due to their extensive interactions with the kinase-specific substrate binding site but often lack necessary pharmacological properties. Chemical modifications of potent peptide inhibitors, such as cyclization, may overcome these drawbacks while maintaining potency. We present an extensive structure-activity relationship (SAR) study of a potent peptide-based PKB/Akt inhibitor. Two backbone cyclic (BC) peptide libraries with varying modes of cyclization, bridge chemistry, and ring size were synthesized and evaluated for in vitro PKB/Akt inhibition. Backbone-to-backbone urea BC peptides were more potent than N-terminus-to-backbone amide BC peptides. Several analogues were up to 10-fold more active than the parent linear peptide. Some activity trends could be rationalized using computational surface mapping of the PKB/Akt kinase catalytic domain. The novel molecules have enhanced pharmacological properties which make them promising lead candidates.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5154-64
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Backbone cyclic peptide inhibitors of protein kinase B (PKB/Akt).
pubmed:affiliation
Institute of Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural