Phage-Display-Derived Peptide Binds to Human CD206 and Modeling Reveals a New Binding Site on the Receptor.

TitlePhage-Display-Derived Peptide Binds to Human CD206 and Modeling Reveals a New Binding Site on the Receptor.
Publication TypeJournal Article
Year of Publication2019
AuthorsAsciutto EK, Kopanchuk S, Lepland A, Simón-Gracia L, Alemán C, Teesalu T, Scodeller P
JournalJ Phys Chem B
Volume123
Issue9
Pagination1973-1982
Date Published2019 Mar 07
ISSN1520-5207
Abstract

We recently identified a tumor-homing peptide (mUNO, sequence: "CSPGAK") that specifically interacts with mouse CD206 to target CD206/MRC1-expressing tumor-associated macrophages in mice. Here, we report studies on the binding of mUNO to human recombinant CD206 (hCD206) and on modeling the mUNO/hCD206 interaction by computational analysis. Fluorescence anisotropy analysis demonstrated that fluorophore-labeled mUNO interacts with hCD206. Microsecond time-scale molecular dynamics simulations and docking predictions showed that mUNO binds to a newly identified epitope between C-type lectin domains 1 and 2. The physical mechanisms that contribute to the docking interactions of mUNO include electrostatic interactions, aromatic interactions, and hydrogen bonds. We also demonstrate the selectivity of FAM-mUNO for CD206-cultured human macrophages. The peptide mUNO appears to be the first ligand capable of interacting with this epitope of hCD206, for which no ligands have been reported. Our study has implications for targeting human M2-like tumor-associated macrophages, a subpopulation of immune cells with a major protumoral role.

DOI10.1021/acs.jpcb.8b11876
Alternate JournalJ Phys Chem B
PubMed ID30768279