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Titolo:
Screening of a library of phage-displayed peptides identifies human Bcl-2 as a taxol binding protein
Autore:
Rodi, DJ; Janes, RW; Sanganee, HJ; Holton, RA; Wallace, BA; Makowski, L;
Indirizzi:
Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA Florida State Univ Tallahassee FL USA 32306 ys, Tallahassee, FL 32306 USA Univndondon Queen Mary & Westfield Coll, Sch Biol Sci, London E1 4NS, Engla Univ London Queen Mary & Westfield Coll London England E1 4NS 4NS, Engla Florida State Univ, Dept Chem, Tallahassee, FL 32306 USA Florida State Univ Tallahassee FL USA 32306 em, Tallahassee, FL 32306 USA Univ London, Birkbeck Coll, Dept Crystallog, London WC1E 7HX, England UnivLondon London England WC1E 7HX Crystallog, London WC1E 7HX, England
Titolo Testata:
JOURNAL OF MOLECULAR BIOLOGY
fascicolo: 1, volume: 285, anno: 1999,
pagine: 197 - 203
SICI:
0022-2836(19990108)285:1<197:SOALOP>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-DEATH; APOPTOSIS; PHOSPHORYLATION; BCL-X(L); PACLITAXEL; MECHANISMS;
Keywords:
phage display; paclitaxel; Bcl-2; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Makowski, L Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA Florida State Univ Tallahassee FL USA 32306 see, FL 32306 USA
Citazione:
D.J. Rodi et al., "Screening of a library of phage-displayed peptides identifies human Bcl-2 as a taxol binding protein", J MOL BIOL, 285(1), 1999, pp. 197-203

Abstract

A random library of phage displayed peptides was screened for binding to abiotinylated derivative of paclitaxel (Taxol). Affinity-selected peptides were analyzed for similarity to human proteins. There was no significant similarity between the paclitaxel-selected peptides and tubulin. However, a subset of the peptides was identified that exhibits significant similarity to a non-conserved region of the anti-apoptotic human protein Bcl-2: ELISA assays confirmed binding of paclitaxel to Bcl-2, and circular dichroism spectroscopy demonstrated that a substantial conformational change accompanies this binding. In vivo, treatment with paclitaxel has been shown to lead to Bcl-2 inactivation with concomitant phosphorylation of residues in a disordered, regulatory loop region of the protein. Similarity between paclitaxel-selected peptides and this loop region implicate these residues in drug binding, and suggest that the apoptotic action of paclitaxel may involve the binding of paclitaxel to Bcl-2. These results demonstrate that peptides displayed on the surface of bacteriophage particles can mimic the ligand-binding properties of disordered regions of proteins. (C) 1999 Academic Press.

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Documento generato il 01/12/20 alle ore 09:48:55