A structure-activity study of a C-terminal endothelin analogue.
We report a structure-activity study of an endothelin (ET) analogue, obtained by introduction of a non-aminoacidic portion on the C-terminal ET pentapeptide. The peptidic moiety was modified with systematic replacement of each residue by alanine (Ala scan); further modifications were performed at the C-terminus. The biological activity was analyzed at both ET(A) and ET(B) receptor subtypes, showing that the two C-terminal residues (Ile-Trp) are very important for the activity. On the contrary, the aminoacidic central portion of the molecule appears to be much more tolerant toward modifications.
Cassano
E
E
Istituto di Mutagenesi e Differenziamento, CNR, Laboratorio Sintesi Peptidica, Pisa, Italy.
Galoppini
C
C
Giusti
L
L
Hamdan
M
M
Macchia
M
M
Mazzoni
M R
MR
Menchini
E
E
Pegoraro
S
S
Rovero
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D016232:Endothelins / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism
D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin