Gross, Andrea and Brox, Regine and Damm, Dominik and Tschammer, Nuska and Schmidt, Barbara and Eichler, Jutta (2015) Ligand selectivity of a synthetic CXCR4 mimetic peptide. BIOORGANIC & MEDICINAL CHEMISTRY, 23 (14). pp. 4050-4055. ISSN 0968-0896, 1464-3391
Full text not available from this repository. (Request a copy)Abstract
The chemokine receptor CXCR4 belongs to the family of seven-transmembrane G-protein coupled receptors (GPCRs). It is activated by its natural ligand SDF-1 alpha. In addition, CXCR4, along with CCR5, serve as coreceptors during HIV-1 entry into its target cell. Recently, we introduced a CXCR4 mimetic peptide, termed CX4-M1, which presents the three extracellular loops (ECLs) of the receptor. CX4-M1 was shown to selectively bind to gp120 of X4-tropic, that is, CXCR4 using, HIV-1, as well as to peptides that present the V3-loops of these gp120 proteins. Furthermore, CX4-M1 selectively inhibits infection of cells with X4-tropic HIV-1. We have now adapted the sequence of the ECLs presented by CX4-M1 to the recently published crystal structure of CXCR4. The binding behavior, as well as the effect on HIV-1 infection, of the resulting peptide (CX4-Mc) was very similar to CX4-M1, validating retrospectively the original design of CX4-M1. A peptide presenting the ECLs of CCR5 (CR5-M), on the other hand, did neither bind to gp120 from X4-tropic HIV-1, nor did it inhibit infection of cells with X4-tropic HIV-1. Furthermore, we could show that CX4-M1, as well as CX4-Mc, but not CR5-M, are selectively recognized by anti-CXCR4 antibodies, bind to SDF-1 alpha, and also inhibit SDF-1 alpha signaling, extending the scope of selective functional CXCR4 mimicry through CX4-M1. (C) 2015 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNODEFICIENCY-VIRUS TYPE-1; 2ND EXTRACELLULAR LOOP; CHEMOKINE RECEPTOR; HIV-1 CORECEPTOR; ENTRY; IDENTIFICATION; INFECTION; LESTR/FUSIN; RESIDUES; TROPISM; CXCR4; GPCR; HIV-1; Peptide; CXCL12/SDF-1 alpha; Receptor mimic |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jul 2019 14:03 |
| Last Modified: | 05 Jul 2019 14:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5209 |
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