Collect. Czech. Chem. Commun. 2000, 65, 407-424

1-Deamino-1(15)-carba and -Dicarba Analogues of Endothelin-1

Jan Hlaváček*, Renáta Marcová, Miloš Buděšínský and Jiřina Slaninová

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


Sulfanyl-methylene and ethylene bridges were inserted into the molecule of endothelin-1 (ET-1) as other possible isosteric replacements of its outer disulfide linkage. The [1-deamino-1-carba]ET-1, [1-deamino-15-carba]ET-1 and [1-deamino-1,15-dicarba]ET-1 were synthesized either by a fragment condensation of protected cyclic pentadecapeptides with carboxy-terminal hexapeptides of the endothelin-1 sequence or by step-wise coupling on polymer support of the entire henicosapeptide sequences from carboxy-terminus. The analogues were devoid of uterotonic activity in comparison with the parent ET-1.

Keywords: Peptides; Solid phase synthesis; Step-wise procedure; Fragment condensation; Endothelin; Disulfide isosters; Uterotonic activity.

References: 37 live references.