title: Characterization of peptide aptamers targeting Bfl-1 anti-apoptotic protein.
abstract: Bfl-1, an anti-apoptotic protein of the Bcl-2 family, has been identified as a potential therapeutic target for B-cell malignancies. We describe herein the first characterization of peptide aptamers selected against Bfl-1. We show that most of the Bfl-1 peptide aptamers do not interact with Bcl-2, Bcl-xL, or Mcl-1 in yeast and that some of them restore the pro-apoptotic activity of Bax in yeast in which Bax and Bfl-1 proteins are coexpressed. When expressed in mammalian cells, peptide aptamers interact with Bfl-1 and sensitize B-cell lines to apoptosis induced by chemotherapeutic agents. We further demonstrate that a nonconstrained peptide derived from one aptamer variable region reverses Bfl-1 anti-apoptotic activity in HeLa cells through disruption of Bax-Bfl-1 interaction. This peptide also promotes cell death in lymphoma B-cell lines expressing a high level of Bfl-1 and sensitizes these cells to drug-induced apoptosis. Taken together, these results further validate Bfl-1 as a therapeutic target for malignant B-cells and suggest that peptide aptamers may be a useful tool for guiding the identification of small compounds that target the anti-apoptotic Bfl-1 protein.
authors.affiliation: Université de Lyon, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Brien
authors.forename: A-L
authors.initials: AL
authors.lastname: Debaud
authors.forename: M
authors.initials: M
authors.lastname: Bickle
authors.forename: M-C
authors.initials: MC
authors.lastname: Trescol-Biemont
authors.forename: O
authors.initials: O
authors.lastname: Moncorge
authors.forename: P
authors.initials: P
authors.lastname: Colas
authors.forename: N
authors.initials: N
authors.lastname: Bonnefoy-Berard
mesh_terms: D017209:Apoptosis; D052158:Aptamers, Peptide / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D052158:Aptamers, Peptide; C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein