| pubmed-article:17199293 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0330390 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0524637 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0288331 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0030956 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0872079 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C1332397 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C1511012 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0205246 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0679199 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C2003941 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:17199293 | lifeskim:mentions | umls-concept:C0243076 | lld:lifeskim |
| pubmed-article:17199293 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:17199293 | pubmed:dateCreated | 2007-1-3 | lld:pubmed |
| pubmed-article:17199293 | pubmed:abstractText | The development of molecules that bind to specific protein surface sites and inhibit protein-protein interactions is a fundamental challenge in molecular recognition. New strategies for approaching this challenge could have important long-term ramifications in biology and medicine. We are exploring the concept that unnatural oligomers with well-defined conformations ("foldamers") can mimic protein secondary structural elements and thereby block specific protein-protein interactions. Here, we describe the identification and analysis of helical peptide-based foldamers that bind to a specific cleft on the anti-apoptotic protein Bcl-xL by mimicking an alpha-helical BH3 domain. Initial studies, employing a fluorescence polarization (FP) competition assay, revealed that among several alpha/beta- and beta-peptide foldamer backbones only alpha/beta-peptides intended to adopt 14/15-helical secondary structure display significant binding to Bcl-xL. The most tightly binding Bcl-xL ligands are chimeric oligomers in which an N-terminal alpha/beta-peptide segment is fused to a C-terminal alpha-peptide segment ((alpha/beta + alpha)-peptides)). Sequence-affinity relationships were probed via standard and nonstandard techniques (alanine scanning and hydrophile scanning, respectively), and the results allowed us to construct a computational model of the ligand/Bcl-xL complex. Analytical ultracentrifugation with a high-affinity (alpha/beta + alpha)-peptide established 1:1 ligand:Bcl-xL stoichiometry under FP assay conditions. Binding selectivity studies with the most potent (alpha/beta + alpha)-peptide, conducted via surface plasmon resonance measurements, revealed that this ligand binds tightly to Bcl-w as well as to Bcl-xL, while binding to Bcl-2 is somewhat weaker. No binding could be detected with Mcl-1. We show that our most potent (alpha/beta + alpha)-peptide can induce cytochrome C release from mitochondria, an early step in apoptosis, in cell lysates, and that this activity is dependent upon inhibition of protein-protein interactions involving Bcl-xL. | lld:pubmed |
| pubmed-article:17199293 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17199293 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17199293 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17199293 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17199293 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17199293 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:17199293 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17199293 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17199293 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:17199293 | pubmed:issn | 0002-7863 | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:UmezawaNaokiN | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:LeeHee-SeungH... | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:GellmanSamuel... | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:WangShaomengS | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:FairlieW... | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:HuangDavid... | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:SadowskyJack... | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:Nikolovska-Co... | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:TomitaYorkY | lld:pubmed |
| pubmed-article:17199293 | pubmed:author | pubmed-author:HadleyErik... | lld:pubmed |
| pubmed-article:17199293 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17199293 | pubmed:day | 10 | lld:pubmed |
| pubmed-article:17199293 | pubmed:volume | 129 | lld:pubmed |
| pubmed-article:17199293 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17199293 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17199293 | pubmed:pagination | 139-54 | lld:pubmed |
| pubmed-article:17199293 | pubmed:dateRevised | 2007-12-3 | lld:pubmed |
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| pubmed-article:17199293 | pubmed:meshHeading | pubmed-meshheading:17199293... | lld:pubmed |
| pubmed-article:17199293 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17199293 | pubmed:articleTitle | (alpha/beta+alpha)-peptide antagonists of BH3 domain/Bcl-x(L) recognition: toward general strategies for foldamer-based inhibition of protein-protein interactions. | lld:pubmed |
| pubmed-article:17199293 | pubmed:affiliation | Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA. | lld:pubmed |
| pubmed-article:17199293 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17199293 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:17199293 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:17199293 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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