TY - JOUR
T1 - Regulation of chemokine recognition by site-specific tyrosine sulfation of receptor peptides
AU - Simpson, Levi S
AU - Zhu, John Z
AU - Widlanski, Theodore S
AU - Stone, Martin J
PY - 2009
Y1 - 2009
N2 - Sulfation of tyrosine is a common posttranslational modification of secreted proteins that influences numerous physiological and pathological processes. Studies of tyrosine sulfation have been hindered by the difficulty of introducing sulfate groups at specific positions of peptides and proteins. Here we report a general strategy for synthesis of peptides containing sulfotyrosine at one or more specific position(s). The approach provides a substantial improvement in both yield and convenience over existing methods. Using synthetic sulfopeptides derived from the chemokine receptor CCR3, we demonstrate that sulfation enhances affinity for the chemokine eotaxin by approximately 7-fold or more than 28-fold, depending on which of two adjacent tyrosine residues is sulfated. The synthetic methodology will substantially enhance efforts to understand the functional and structural consequences of protein tyrosine sulfation.
AB - Sulfation of tyrosine is a common posttranslational modification of secreted proteins that influences numerous physiological and pathological processes. Studies of tyrosine sulfation have been hindered by the difficulty of introducing sulfate groups at specific positions of peptides and proteins. Here we report a general strategy for synthesis of peptides containing sulfotyrosine at one or more specific position(s). The approach provides a substantial improvement in both yield and convenience over existing methods. Using synthetic sulfopeptides derived from the chemokine receptor CCR3, we demonstrate that sulfation enhances affinity for the chemokine eotaxin by approximately 7-fold or more than 28-fold, depending on which of two adjacent tyrosine residues is sulfated. The synthetic methodology will substantially enhance efforts to understand the functional and structural consequences of protein tyrosine sulfation.
UR - http://www.ncbi.nlm.nih.gov/pubmed/19246006
U2 - 10.1016/j.chembiol.2008.12.007
DO - 10.1016/j.chembiol.2008.12.007
M3 - Article
VL - 16
SP - 153
EP - 161
JO - Chemistry and Biology
JF - Chemistry and Biology
SN - 1074-5521
IS - 2
ER -