Exploring the potential of CXCR4 mimetic peptides to target cancer cells

The chemokine receptor CXCR4 plays crucial roles in various physiological processes and is implicated in diseases such as HIV-1 infection and cancer 1 .In cancer, the interaction between CXCR4 and the chemokine CXCL12 has been shown to stimulate multiple oncogenic processes 2 .In HIV-1 infection, CXCR4 serves as a coreceptor for viral entry into the host cell 3 .Previously, we designed a peptide that presents the three extracellular loops (ECLs) of CXCR4, which was shown to inhibit both HIV-1 infection 4 and CXCR4 signaling 5 .We have now optimized the sequence of this peptide, CX4M1, to enhance its affinity for CXCL12 by truncation, among other modifications.The optimized CX4M1 variants bind to CXCL12 with higher affinity while being considerably shorter than the original peptide.These peptides have been shown to interfere with the migration of CXCR4dependent cancer cells and inhibit the binding of CXCL12 to CXCR4-expressing cancer cells. Further truncation to find minimal active peptide length Investigating the CXCR4 mimetic peptides in an in vivo model Introducing the N-terminal tail as a CXCR4 mimetic peptide testing in cancer cell based assays