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