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Journal of Biomolecular Screening
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A New Peptidic Vector for Molecular Imaging of Apoptosis, Identified by Phage Display Technology

Catherine Laumonier

Jérôme Segers

Sophie Laurent

Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, Mons, Belgium

Alain Michel

Laboratory of Proteomic and Protein Chemistry, University of Mons-Hainaut, Mons, Belgium

Frédérique Coppée

Alexandra Belayew

Laboratory of Molecular Biology, University of Mons-Hainaut, Mons, Belgium

Luce Vander Elst

Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, Mons, Belgium

Robert N. Muller

Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut 24, Avenue du Champ de Mars, B-7000 Mons, Belgium robert.muller{at}umh.ac.be

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 6.08 x 1010 M to 1.62 x 1011M. 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) x 1011M. 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. (Journal of Biomolecular Screening 2006:537-545)

Key Words: phage display • apoptosis • phosphatidylserine • MRI • contrast agent

This version was published on August 1, 2006

Journal of Biomolecular Screening, Vol. 11, No. 5, 537-545 (2006)
DOI: 10.1177/1087057106288220
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