Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

Journal Article · · PLoS ONE
 [1];  [2];  [2]
  1. Washington Univ., St. Louis, MO (United States); Univ. of Pittsburgh, PA
  2. Univ. of Pittsburgh, PA (United States)

The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, highstringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD ~1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy.

Research Organization:
Washington Univ., St. Louis, MO (United States)
Sponsoring Organization:
USDOE Office of Science (SC); USDOD
Grant/Contract Number:
SC0002032
OSTI ID:
1904543
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 7 Vol. 8; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (50)

Sequential SPECT and Optical Imaging of Experimental Models of Prostate Cancer with a Dual Modality Inhibitor of the Prostate-Specific Membrane Antigen journal August 2011
Iterative In Situ Click Chemistry Creates Antibody-like Protein-Capture Agents journal June 2009
Bio-Inspired Design and Potential Biomedical Applications of a Novel Class of High-Affinity Peptides journal January 2012
Correspondence Re: Ghosh A and Heston WDW. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem 91:528-539, 2004 journal October 2004
High level PSMA expression is associated with early psa recurrence in surgically treated prostate cancer journal August 2010
Construction of High-Complexity Combinatorial Phage Display Peptide Libraries journal February 2001
A low molecular weight PSMA-based fluorescent imaging agent for cancer journal December 2009
Rapid identification of improved protein ligands using peptoid microarrays journal July 2009
Modulation of nuclear internalization of Tat peptides by fluorescent dyes and receptor-avid peptides journal April 2007
Re: Screening for Prostate Cancer with Prostate-Specific Antigen Testing: American Society of Clinical Oncology Provisional Clinical Opinion journal February 2013
Prostate-specific antigen velocity at low prostate-specific antigen levels as screening tool for prostate cancer: results of second screening round of ERSPC (ROTTERDAM) journal February 2004
Virus–Polymer Hybrid Nanowires Tailored to Detect Prostate-Specific Membrane Antigen journal March 2012
Radiohalogenated Prostate-Specific Membrane Antigen (PSMA)-Based Ureas as Imaging Agents for Prostate Cancer journal December 2008
PSMA mimotope isolated from phage displayed peptide library can induce PSMA specific immune response journal December 1999
Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer journal February 2006
Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase journal April 2005
Engineered antibody Fc variants with enhanced effector function journal March 2006
A Dimeric Peptide That Binds Selectively to Prostate-Specific Membrane Antigen and Inhibits its Enzymatic Activity journal September 2006
Phase I Evaluation of J591 as a Vascular Targeting Agent in Progressive Solid Tumors journal May 2007
2-(3-{1-Carboxy-5-[(6-[18F]Fluoro-Pyridine-3-Carbonyl)-Amino]-Pentyl}-Ureido)-Pentanedioic Acid, [18F]DCFPyL, a PSMA-Based PET Imaging Agent for Prostate Cancer journal December 2011
An AlphaScreen™-Based High-Throughput Screen to Identify Inhibitors of Hsp90-Cochaperone Interaction journal March 2009
Screening for Inhibitors of Low-Affinity Epigenetic Peptide-Protein Interactions: An AlphaScreen™-Based Assay for Antagonists of Methyl-Lysine Binding Proteins journal December 2009
Indium-111–Capromab Pendetide Radioimmunoscintigraphy and Prognosis for Durable Biochemical Response to Salvage Radiation Therapy in Men After Failed Prostatectomy journal May 2003
Monoclonal Antibody Therapy for Prostate Cancer: Finally a Reality? journal July 2004
Phase I Trial of 177 Lutetium-Labeled J591, a Monoclonal Antibody to Prostate-Specific Membrane Antigen, in Patients With Androgen-Independent Prostate Cancer journal July 2005
Applicability of biomarkers in the early diagnosis of prostate cancer journal July 2004
A Modular Strategy to Prepare Multivalent Inhibitors of Prostate-Specific Membrane Antigen (PSMA) journal December 2011
High-affinity Near-infrared Fluorescent Small-molecule Contrast Agents for In Vivo Imaging of Prostate-specific Membrane Antigen journal October 2005
Sequential SPECT and Optical Imaging of Experimental Models of Prostate Cancer with a Dual Modality Inhibitor of the Prostate-Specific Membrane Antigen journal August 2011
Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer journal January 2004
Radiotracer II: Peptide-Based Radiopharmaceuticals book January 2011
[1] Affinity maturation of phage-displayed peptide ligands book January 1996
68 Ga-Labeled Inhibitors of Prostate-Specific Membrane Antigen (PSMA) for Imaging Prostate Cancer journal July 2010
Synthesis and Evaluation of Technetium-99m- and Rhenium-Labeled Inhibitors of the Prostate-Specific Membrane Antigen (PSMA) journal July 2008
Prevalence of Prostate Cancer among Men with a Prostate-Specific Antigen Level ≤4.0 ng per Milliliter journal May 2004
A homogeneous method for investigation of methylation-dependent protein-protein interactions in epigenetics journal November 2009
A Dimeric Peptide That Binds Selectively to Prostate-Specific Membrane Antigen and Inhibits its Enzymatic Activity journal September 2006
Preclinical Evaluation of Novel Glutamate-Urea-Lysine Analogues That Target Prostate-Specific Membrane Antigen as Molecular Imaging Pharmaceuticals for Prostate Cancer journal August 2009
Pilot Trial of Unlabeled and Indium-111–Labeled Anti–Prostate-Specific Membrane Antigen Antibody J591 for Castrate Metastatic Prostate Cancer journal October 2005
Phase I Evaluation of J591 as a Vascular Targeting Agent in Progressive Solid Tumors journal May 2007
2-(3-{1-Carboxy-5-[(6-[18F]Fluoro-Pyridine-3-Carbonyl)-Amino]-Pentyl}-Ureido)-Pentanedioic Acid, [18F]DCFPyL, a PSMA-Based PET Imaging Agent for Prostate Cancer journal December 2011
Disulfide-constrained peptides that bind to the extracellular portion of the prostate-specific membrane antigen journal May 2004
Synthesis and characterization of a high-affinity  v 6-specific ligand for in vitro and in vivo applications journal May 2009
Phase I Trial of Yttrium-90—Labeled Anti—Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Androgen-Independent Prostate Cancer journal July 2004
The Prognostic Significance of Indium-111–Capromab Penetide journal January 2004
Phase I Trial of 177 Lutetium-Labeled J591, a Monoclonal Antibody to Prostate-Specific Membrane Antigen, in Patients With Androgen-Independent Prostate Cancer journal July 2005
Screening for Prostate Cancer With Prostate-Specific Antigen Testing: American Society of Clinical Oncology Provisional Clinical Opinion journal August 2012
Prostate-Specific Antigen Test for Prostate Cancer Screening: American Society of Clinical Oncology Provisional Clinical Opinion journal September 2012
Discovery of High-Affinity Protein Binding Ligands – Backwards journal May 2010
In Vivo Selection of Phage for the Optical Imaging of PC-3 Human Prostate Carcinoma in Mice journal September 2006

Cited By (2)

Size Matters: Arginine-Derived Peptides Targeting the PSMA Receptor Can Efficiently Complex but Not Transfect siRNA journal December 2019
Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins journal January 2016

Similar Records

Trinucleotide cassettes increase diversity of T7 phage-displayed peptide library
Journal Article · Fri Oct 05 00:00:00 EDT 2007 · BMC Biotechnology (Online) · OSTI ID:1626539

Screening a phage display library for a novel FGF8b-binding peptide with anti-tumor effect on prostate cancer
Journal Article · Wed May 01 00:00:00 EDT 2013 · Experimental Cell Research · OSTI ID:22278236

Blocking peptides against HBV: PreS1 protein selected from a phage display library
Journal Article · Fri Sep 09 00:00:00 EDT 2011 · Biochemical and Biophysical Research Communications · OSTI ID:22207486