Targeting phosphatidylserine on apoptotic cells with phages and peptides selected from a bacteriophage display library.
Phosphatidylserine (PS) is a well-characterized biomarker for apoptosis. Ligands that bind to PS can be used for noninvasive imaging of therapy-induced cell death, particularly apoptosis. In this study, we screened a random 12-mer peptide phage library on liposomes prepared from PS. One clone displaying the peptide SVSVGMKPSPRP (designated as PS3-10) bound to PS approximately 4-fold better than its binding to phosphatidylcholine and 18-fold better than to bovine serum albumin in a solid-phase binding assay. In addition, the binding of the corresponding PS3-10 peptide to PS was significantly higher than that of a scrambled peptide. PS3-10 phages, but not a control 4-2-2 phage, bound to aged red blood cells that had PS exposed on their surface. Binding of PS3-10 phages and PS3-10 peptide to TRAIL-induced apoptotic DLD1 cells was 3.2 and 5.4 times higher than their binding to untreated viable cells, respectively. Significantly, immunohistochemical staining confirmed selective binding of PS3-10 phages to apoptotic cells. Our data suggest that panning of phage display libraries may allow the selection of suitable peptide ligands for apoptotic cells and that PS3-10 peptide may serve as a template for further development of molecular probes for in vitro and in vivo imaging of apoptosis.
Department of Experimental Diagnostic Imageing, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Ruping
R
Shao
Chiyi
C
Xiong
Xiaoxia
X
Wen
Juri G
JG
Gelovani
Chun
C
Li
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D017104:Bacteriophage M13 / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology; D003952:Diagnostic Imaging / Q000379:methods*; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000032:analysis / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D019151:Peptide Library; D010455:Peptides; D010718:Phosphatidylserines; D053221:TNF-Related Apoptosis-Inducing Ligand