Abstract
One of the greatest challenges in fighting cancer is cell targeting and biomarker selection. The Atypical Chemokine Receptor ACKR3/CXCR7 is expressed on many cancer cell types, including breast cancer and glioblastoma, and binds the endogenous ligands SDF1/CXCL12 and ITAC/CXCL11. A 20 amino acid region of the ACKR3/CXCR7 N-terminus was synthesized and targeted with the NEB PhD™-7 Phage Display Peptide Library. Twenty-nine phages were isolated and heptapeptide inserts sequenced; of these, 23 sequences were unique. A 3D molecular model was created for the ACKR3/CXCR7 N-terminus by mutating the corresponding region of the crystal structure of CXCR4 with bound SDF1/CXCL12. A ClustalW alignment was performed on each peptide sequence using the entire SDF1/CXCL12 sequence as the template. The 23-peptide sequences showed similarity to three distinct regions of the SDF1/CXCL12 molecule. A 3D molecular model was made for each of the phage peptide inserts to visually identify potential areas of steric interference of peptides that simulated CXCL12 regions not in contact with the receptor’s Nterminus. An ELISA analysis of the relative binding affinity between the peptides identified 9 peptides with statistically significant results. The candidate pool of 9 peptides was further reduced to 3 peptides based on their affinity for the targeted N-terminus region peptide versus no target peptide present or a scrambled negative control peptide. The results clearly show the Phage Display protocol can be used to target a synthesized region of the ACKR3/CXCR7 N-terminus. The 3 peptides chosen, P20, P3, and P9, will be the basis for further targeting studies.
Keywords: Atypical chemokine receptor, Glioblastoma, Phage Display, Targeted therapy.
Current Topics in Medicinal Chemistry
Title:Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization
Volume: 16 Issue: 13
Author(s): R.D. Vestal, D.R. LaJeunesse and E.W. Taylor
Affiliation:
Keywords: Atypical chemokine receptor, Glioblastoma, Phage Display, Targeted therapy.
Abstract: One of the greatest challenges in fighting cancer is cell targeting and biomarker selection. The Atypical Chemokine Receptor ACKR3/CXCR7 is expressed on many cancer cell types, including breast cancer and glioblastoma, and binds the endogenous ligands SDF1/CXCL12 and ITAC/CXCL11. A 20 amino acid region of the ACKR3/CXCR7 N-terminus was synthesized and targeted with the NEB PhD™-7 Phage Display Peptide Library. Twenty-nine phages were isolated and heptapeptide inserts sequenced; of these, 23 sequences were unique. A 3D molecular model was created for the ACKR3/CXCR7 N-terminus by mutating the corresponding region of the crystal structure of CXCR4 with bound SDF1/CXCL12. A ClustalW alignment was performed on each peptide sequence using the entire SDF1/CXCL12 sequence as the template. The 23-peptide sequences showed similarity to three distinct regions of the SDF1/CXCL12 molecule. A 3D molecular model was made for each of the phage peptide inserts to visually identify potential areas of steric interference of peptides that simulated CXCL12 regions not in contact with the receptor’s Nterminus. An ELISA analysis of the relative binding affinity between the peptides identified 9 peptides with statistically significant results. The candidate pool of 9 peptides was further reduced to 3 peptides based on their affinity for the targeted N-terminus region peptide versus no target peptide present or a scrambled negative control peptide. The results clearly show the Phage Display protocol can be used to target a synthesized region of the ACKR3/CXCR7 N-terminus. The 3 peptides chosen, P20, P3, and P9, will be the basis for further targeting studies.
Export Options
About this article
Cite this article as:
Vestal R.D., LaJeunesse D.R. and Taylor E.W., Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization, Current Topics in Medicinal Chemistry 2016; 16 (13) . https://dx.doi.org/10.2174/1568026615666150915120037
DOI https://dx.doi.org/10.2174/1568026615666150915120037 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
PLK1 Inhibition Radiosensitizes Breast Cancer Cells, but Shows Low Efficacy as Monotherapy or in Combination with other Cytotoxic Drugs
Anti-Cancer Agents in Medicinal Chemistry Recent Developments on 1,2,4-Triazole Nucleus in Anticancer Compounds: A Review
Anti-Cancer Agents in Medicinal Chemistry RNA Splicing: Basic Aspects Underlie Antitumor Targeting
Recent Patents on Anti-Cancer Drug Discovery Deregulation of HOX B13 Expression in Urinary Bladder Cancer Progression
Current Medicinal Chemistry Going 3D – Cell Culture Approaches for Stem Cell Research and Therapy
Current Tissue Engineering (Discontinued) Small and Long Non-Coding RNAs: Novel Targets in Perspective Cancer Therapy
Current Genomics Cancer Therapeutics: Emerging Targets and Trends
Current Cancer Therapy Reviews Current Evaluation of the Millennium Phytomedicine- Ginseng (II): Collected Chemical Entities, Modern Pharmacology, and Clinical Applications Emanated from Traditional Chinese Medicine
Current Medicinal Chemistry Phytochemistry and Pharmacognosy of Naturally Occurring Prenyloxyanthraquinones
Current Drug Targets The Potency of Refined Mouse Models: Implications for Clinical Trials
Current Cancer Therapy Reviews RNA Silencing: Recent Developments on miRNAs
Recent Patents on DNA & Gene Sequences Dysfunctions of the Diffusional Membrane Pathways Mediated Hemichannels in Inherited and Acquired Human Diseases
Current Vascular Pharmacology Resistance to Radiotherapy and Targeted Molecular Therapies in Squamous Cell Carcinomas of the Head and Neck, Preclinical Data and New Approaches
Current Signal Transduction Therapy Screening for Infectious Diseases During Pregnancy: Which Test and Which Situation
Current Women`s Health Reviews Hecogenin Acetate Inhibits Reactive Oxygen Species Production and Induces Cell Cycle Arrest and Senescence in the A549 Human Lung Cancer Cell Line
Anti-Cancer Agents in Medicinal Chemistry Immune Modulation of Asian Folk Herbal Medicines and Related Chemical Components for Cancer Management
Current Medicinal Chemistry Cancer Invasion and Metastasis: Discovering New Targets For Diagnosis and Therapeutics
Current Signal Transduction Therapy CycloSal-dRFIB, a Thymidine Mimetic, Thymidine Kinase by-Pass Nucleoside Prodrug: Radioiodination, in vitro Cellular Uptake and Biodistribution in Murine Models
Current Radiopharmaceuticals An Overview on Keratinocyte Growth Factor: From the Molecular Properties to Clinical Applications
Protein & Peptide Letters Radionuclide Molecular Imaging Using Affibody Molecules
Current Pharmaceutical Biotechnology