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.
Shao
Ruping
R
Department of Experimental Diagnostic Imageing, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Xiong
Chiyi
C
Wen
Xiaoxia
X
Gelovani
Juri G
JG
Li
Chun
C
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