Synthesis and structure-activity relationship studies of new endothelin pseudopeptide analogues containing alkyl spacers.
We replaced the Asp18-Ile19 dipeptide of the C-terminal ET analogue Ph-Ph-CH2-O-N=CH-CO-Phe-Asp-Ile-Ile-Trp-OH by alkyl spacers of various lengths to investigate the role of the aminoacidic central portion of the molecule and to define the N-terminal and C-terminal pharmacophoric regions of this analogue. The side-chains of the central dipeptide have been shown to be irrelevant for the binding of the molecule to the receptor, but the distance between the two postulated sites of interaction of the ligand with the ETB receptor appears to be fundamental.
Galoppini
C
C
CNR-IMD, Laboratorio Sintesi Peptidica, Pisa, Italy.
Giusti
L
L
Macchia
M
M
Hamdan
M
M
Mazzoni
M R
MR
Calvani
F
F
Rovero
P
P
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000737:chemistry*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D013329:Structure-Activity Relationship
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D008024:Ligands; D010446:Peptide Fragments; D044023:Receptor, Endothelin B