Novel small synthetic HIV-1 V3 crown variants: CCR5 targeting ligands

Abstract

The CCR5 antagonism represents a promising pharmacological strategy for therapeutic intervention, as it plays a significant role in reducing the severity and progression of a wide range of pathological conditions. Here we designed and generated peptide ligands targeting the chemokine receptor; CCR5 that were derived from the critical interaction sites of the V3 crown domain of envelope protein glycoprotein gp120 (TRKSIHIGPGRAFYTTGEI) of HIV-1 using computational biology approach and the peptide sequence corresponding to this region was taken as the template peptide, designated as TMP-1. The peptide variants were synthesized by employing Fmoc chemistry using polymer support and were labelled with Rhodamine B to study their interaction with the CCR5 receptor expressed on various cells. TMP-1 and TMP-2 were selected as the high-affinity ligands from in vitro receptor binding assays. Specific receptor binding experiments in activated peripheral blood mononuclear cells (PBMCs) and HOS.CCR5 cells indicated that TMP-1 and TMP-2 had significant CCR5 specificity. Further, the functional analysis of TMP peptides using chemotactic migration assay showed that both peptides did not mediate the migration of responsive cells. Thus TMP-1 and TMP-2 represent promising CCR5 targeting peptide candidates.

Oncogenic Proteomics Approaches for Translational Research and HIV-Associated Malignancy Mechanisms

“…CXCR4 and CCR5 are chemokine receptors and members of the G-protein-coupled class family; they have the role of mediating leukocyte development, trafficking, angiogenesis, and immune response [ 126 ]. CXCR4 and CCR4 are attractive candidates for cancer studies since they have been reported to modulate physiological processes associated with proliferation, survival, tumor growth, invasions, and epidermal growth factor receptors [ 127 , 128 ]. CXCR4 has been a consistent marker throughout predominant oncological diseases, including lung cancer [ 129 , 130 ] and PCa [ 131 ].…”