A new peptidic vector for molecular imaging of apoptosis, identified by phage display technology.
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.
Laumonier
Catherine
C
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, Mons, Belgium.
Segers
Jérôme
J
Laurent
Sophie
S
Michel
Alain
A
Coppée
Frédérique
F
Belayew
Alexandra
A
Elst
Luce Vander
LV
Muller
Robert N
RN
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
D017304:Annexin A5; D003287:Contrast Media; D019151:Peptide Library; D010455:Peptides; D010718:Phosphatidylserines