TY - JOUR
T1 - Structure-activity relationships of endothelin
T2 - Importance of the C-terminal moiety
AU - Kimura, Sadao
AU - Kasuya, Yoshitoshi
AU - Sawamura, Tatsuya
AU - Shinmi, Osamu
AU - Sugita, Yoshiki
AU - Yanagisawa, Masashi
AU - Goto, Katsutoshi
AU - Masaki, Tomoh
N1 - Funding Information:
ACKNOWLEDGMENTS: We thank Ms. Lisa G. Bond for reading the manuscript, and Drs S. Sakakibara, M. Fujino and C. Kitada for the synthesis of ET. This work was supported in part by grants from the University of Tsukuba Project Research and the Ministry of Education, Science and Culture of Japan.
PY - 1988/11/15
Y1 - 1988/11/15
N2 - The vasoconstrictor activities of various forms of derivatives of endothelin (ET) were characterized in vitro by measuring the contraction of porcine coronary artery strips. The removal of the C-terminal Trp21 reduced the molar potency of the peptide by nearly 3 orders of magnitude. The removal of amino acid residues from the C-terminus of ET(1-20) further attenuated the activity. Replacement of Trp21 with D-Trp, reduction and carboxamidomethylation of the four Cys residues, or cleavage at Lys9 by lysyl endopeptidase all lowered the potency approximately 200 fold. While both native ET and [D-Trp21]ET induced a very slow and sustained vasoconstriction, the other derivatives of ET listed above showed a much more rapid kinetics of vasoconstriction. These results indicate that the C-terminal Trp of ET is especially important for the potent and extremely long-lasting vasoconstrictor activity characteristic to ET.
AB - The vasoconstrictor activities of various forms of derivatives of endothelin (ET) were characterized in vitro by measuring the contraction of porcine coronary artery strips. The removal of the C-terminal Trp21 reduced the molar potency of the peptide by nearly 3 orders of magnitude. The removal of amino acid residues from the C-terminus of ET(1-20) further attenuated the activity. Replacement of Trp21 with D-Trp, reduction and carboxamidomethylation of the four Cys residues, or cleavage at Lys9 by lysyl endopeptidase all lowered the potency approximately 200 fold. While both native ET and [D-Trp21]ET induced a very slow and sustained vasoconstriction, the other derivatives of ET listed above showed a much more rapid kinetics of vasoconstriction. These results indicate that the C-terminal Trp of ET is especially important for the potent and extremely long-lasting vasoconstrictor activity characteristic to ET.
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U2 - 10.1016/S0006-291X(88)80757-5
DO - 10.1016/S0006-291X(88)80757-5
M3 - Article
C2 - 3056409
AN - SCOPUS:0023820841
SN - 0006-291X
VL - 156
SP - 1182
EP - 1186
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -