title: A new peptidic vector for molecular imaging of apoptosis, identified by phage display technology.
abstract: Phosphatidylserine (PS) exposure on the cell surface is an early marker of apoptosis. To select PS binding peptides as vectors of contrast agents to image apoptosis, a phage library has been exposed to perfused mouse livers. Phages not retained on control livers during the first perfusions were used for selections on apoptotic livers in a second series of perfusions. Four selected phages were further evaluated for binding to PS-coated enzyme-linked immunosorbent assay (ELISA) plates. They presented an apparent affinity constant (Ka app) for PS ranging from 6.08x10(10) M to 1.62x10(11)M. These phages did not bind to phosphatidylcholine, and competition with annexin V confirmed their specific interaction with PS. The phage with the highest affinity-bound PS in ELISA with a Ka app=(1.6+/-0.2)x10(11)M. It carried the TLVSSL peptide that was synthesized. Specific competition with annexin V and with the synthetic peptide was performed and confirms the specificity of the interaction.
authors.affiliation: Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, Mons, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Laumonier
authors.forename: Jérôme
authors.initials: J
authors.lastname: Segers
authors.forename: Sophie
authors.initials: S
authors.lastname: Laurent
authors.forename: Alain
authors.initials: A
authors.lastname: Michel
authors.forename: Frédérique
authors.initials: F
authors.lastname: Coppée
authors.forename: Alexandra
authors.initials: A
authors.lastname: Belayew
authors.forename: Luce Vander
authors.initials: LV
authors.lastname: Elst
authors.forename: Robert N
authors.initials: RN
authors.lastname: Muller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D017104:Bacteriophage M13 / Q000378:metabolism; D001667:Binding, Competitive; D003287:Contrast Media / Q000302:isolation & purification*; D003952:Diagnostic Imaging; D008099:Liver / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D019151:Peptide Library; D010455:Peptides / Q000302:isolation & purification*; D010477:Perfusion / Q000379:methods; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding
chemical_list: D017304:Annexin A5; D003287:Contrast Media; D019151:Peptide Library; D010455:Peptides; D010718:Phosphatidylserines