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Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and
R D Vestal1, D R LaJeunesse, E W Taylor
1Department of Nanoscience, University of North Carolina at Greensboro (UNCG), Greensboro, North Carolina 27412, USA..
Current Topics in Medicinal Chemistry
|September 16, 2015
Summary
Researchers developed a phage display method to identify peptides targeting the ACKR3/CXCR7 receptor, crucial for cancer cell targeting. Three promising peptides (P20, P3, P9) were identified for future cancer therapy development.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Targeting cancer cells and identifying biomarkers remain significant challenges in oncology.
- The Atypical Chemokine Receptor ACKR3/CXCR7 is expressed in various cancer types, including breast cancer and glioblastoma.
- ACKR3/CXCR7 binds endogenous ligands such as SDF1/CXCL12 and ITAC/CXCL11.
Purpose of the Study:
- To synthesize a region of the ACKR3/CXCR7 N-terminus and target it using a phage display peptide library.
- To identify specific peptides that bind to the ACKR3/CXCR7 N-terminus for potential cancer targeting applications.
Main Methods:
- A 20 amino acid region of the ACKR3/CXCR7 N-terminus was synthesized and used to screen the NEB PhD-7 Phage Display Peptide Library.
- Isolated phage heptapeptide inserts were sequenced, and 3D molecular models were generated for the ACKR3/CXCR7 N-terminus and peptide inserts.
- ELISA analysis was performed to determine the binding affinity of the identified peptides to the target N-terminus region.
Main Results:
- Twenty-nine phages were isolated, yielding 23 unique heptapeptide sequences.
- Sequence alignment revealed similarities between peptides and three distinct regions of the SDF1/CXCL12 molecule.
- ELISA identified 9 peptides with significant binding affinity, further narrowed down to 3 peptides (P20, P3, P9) with high specificity.
Conclusions:
- The Phage Display protocol is effective for targeting synthesized regions of the ACKR3/CXCR7 N-terminus.
- The identified peptides P20, P3, and P9 demonstrate potential as novel agents for ACKR3/CXCR7-mediated cancer targeting.
- These peptides provide a foundation for further development in cancer therapy strategies.
