The Synthesis of Sulfated CCR5 Peptide Surrogates and their Use to Study Receptor-Ligand Interactions

Title:The Synthesis of Sulfated CCR5 Peptide Surrogates and their Use to Study Receptor-Ligand Interactions

Volume: 25 Issue: 12

Author(s): Fred Naider*Jacob Anglister

Affiliation:

• Department of Chemistry and Macromolecular Assembly Institute, College of Staten Island of the City University of New York, Staten Island, New York 10314,United States

Keywords: Chemokine receptors, gp120-CCR5 interactions, peptide surrogates, protein-peptide complexes, sulfated tyrosine, solid phase peptide synthesis.

Abstract: Background: Tyrosine sulfation is an important post-translational modification of secreted and membrane proteins in multi-cellular organisms. This modification is catalyzed by tyrosylprotein sulfotransferases that often modify tyrosine residues in their target substrates in a heterogeneous manner. Chemokine receptors such as CCR5, which play roles in inflammation, immunity and viral infection, are sulfated on tyrosine residues in their extracellular N-termini. The heterogeneity of the sulfation has made it difficult to obtain atomic-resolution information on this region of CCR5. Homogeneously sulfated peptide surrogates can be efficiently synthesized by chemical and biochemical approaches. This communication reviews current chemical and biochemical methods for peptide tyrosine sulfation and the use of N-terminal CCR5 peptide surrogates in biochemical and structural analyses.

Conclusion: Using solid phase peptide synthesis and synthons containing sulfotyrosine or sulfotyrosine neopentyl esters peptides containing up to 30 residues with multiple sulfotyrosines can be synthesized and purified in high (>50-70%) yield. Such peptides can be isotopically labeled at selected positions and used in detailed NMR investigations to investigate the interactions of sulfotyrosine residues with receptors. The application of transferred NOE studies to investigate CCL5/CCR5 interactions has led to the determination of pairwise interactions between the chemokine and its receptor.

Cite this article as:

Naider Fred *, Anglister Jacob , The Synthesis of Sulfated CCR5 Peptide Surrogates and their Use to Study Receptor-Ligand Interactions, Protein & Peptide Letters 2018; 25 (12) . https://dx.doi.org/10.2174/0929866525666181101103834