Structural and Biological Characterizations of Novel High-Affinity Fluorescent Probes with Overlapped and Distinctive Binding Regions on CXCR4

Clicks: 334
ID: 4719
1970
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Star

Ranked #195 of 729 articles by views in molecules

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 729 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
CXC-type chemokine receptor 4 (CXCR4) is well known as a co-receptor for cellular entry and infection of human immunodeficiency virus type 1 (HIV-1). As an important member of the G protein-coupled receptor (GPCR) family, CXCR4 also mediates a variety of cellular processes and functions, such as cell chemotaxis, proliferation, and calcium signal transductions. Identification and characterization of molecular ligands or probes of CXCR4 have been an intensive area of investigations as such ligands or probes are of significant clinical values for the studies and treatments of HIV-1 infection and other human diseases mediated by the receptor. The crystal structures of CXCR4 in complex with different ligands have revealed two distinctive binding regions or subpockets. Thus, understanding the interactions of diverse ligands with these distinctive CXCR4 binding regions has become vital for elucidating the relationship between binding modes and biological mechanisms of ligand actions. Peptidic CVX15 is the only ligand that has been validated to bind one of these distinctive binding regions (or so called the major subpocket) of CXCR4. Therefore, in this study, we developed an efficient probe system including two high-affinity peptidic fluorescent probes, designated as FITC-CVX15 and FITC-DV1, with the aim of targeting distinctive CXCR4 subpockets. We conducted rational design and chemical characterization of the two CXCR4-specific probes and examined their application in biological experiments including competitive binding assays, flow cytometry analysis, and confocal imaging. Especially these two probes were applied in parallel CXCR4 competitive binding assays to detect and analyze potential binding modes of diverse CXCR4 ligands, together with molecular docking and simulations. Our results have indicated that these peptidic fluorescent probe systems provide novel ligand detecting tools, as well as present a new approach for analyzing distinctive binding modes of diverse CXCR4 ligands.
Reference Key
siyu1970structuralmolecules Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Siyu Zhu;Qian Meng;Robert T. Schooley;Jing An;Yan Xu;Ziwei Huang;Zhu, Siyu;Meng, Qian;Schooley, Robert T.;An, Jing;Xu, Yan;Huang, Ziwei and
Journal molecules
Year 1970
DOI
10.3390/molecules24162928
URL
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.