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The chemical synthesis and binding affinity to the EGF receptor of the EGF‐like domain of heparin‐binding EGF‐like growth factor (HB‐EGF)
Author(s) -
Shin Song Yub,
Yokoyama Tetsuo,
Takenouchi Takato,
Munekata Eisuke
Publication year - 2003
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.450
Subject(s) - heparin binding egf like growth factor , epidermal growth factor , egf like domain , receptor , chemistry , binding domain , biochemistry , binding site , biology , microbiology and biotechnology
Heparin‐binding EGF‐like growth factor (HB‐EGF), which belongs to the EGF‐family of growth factors, was isolated from the conditioned medium of macrophage‐like cells. To investigate the effect of N ‐ and C ‐terminal residues of the EGF‐like domain of HB‐EGF in the binding affinity to the EGF receptor on A431 cell. We synthesized HB‐EGF(44–86) corresponding to the EGF‐like domain of HB‐EGF and its N ‐ or C ‐terminal truncated peptides. Thermolytic digestion demonstrated three disulfide bond pairings of the EGF‐like domain in HB‐EGF is consistent with that of human‐EGF and human‐TGF‐α. HB‐EGF(44–86) showed high binding affinity to EGF‐receptor, like human‐EGF. The truncation of the C ‐terminal Leu 86 residue from HB‐EGF(44–86), HB‐EGF(45–86) or HB‐EGF(46–86) caused a drastic reduction in the binding affinity to the EGF receptor. These results suggest that the EGF‐like domain of HB‐EGF plays an important role in the binding to the EGF receptor, and its C ‐terminal Leu 86 residue is necessary for binding with the EGF‐receptor. In addition, the deletion of the two N ‐terminal residues (Asp 44 ‐Pro 45 ) from HB‐EGF(44–86) caused a 10‐fold decrease in relative binding affinity to the EGF receptor. This indicates that the two N ‐terminal residues of the EGF‐like domain of HB‐EGF are necessary for its optimal binding affinity to the EGF receptor. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.