Cyclic angiotensin analogs

摘要

The invention relates to analogs of angiotensins, in particular to cyclised analogs having Ang(1-8) agonistic or antagonistic activity and to cyclised Ang(1-7) analogs with agonistic or antagonistic activity and displaying improved proteolytic resistance compared to their linear counterparts. Provided is a cyclic angiotensin peptide analog comprising a thioether-bridge linkage between the amino acids corresponding to positions Tyr4 and Pro7 in naturally occurring Angiotensin. Also provided is the use of analogs in therapy, for example hypertension.

主权项

1. A cyclic peptide analog of Angiotensin I (Ang(1-10)), Angiotensin II (Ang(1-8)), Angiotensin III (Ang(2-8)), Angiotensin IV (Ang(3-8)), Ang(1-7), Ang(2-7) or Ang(1-9), comprising a thioether-bridge linkage between the side chains of the amino acids corresponding to positions Tyr4 and Pro7 in naturally occurring Angiotensin,said analog consisting of the general formula [Cyc4-7]Xaa1-10, [Cyc4-7]Xaa1-9, [Cyc4-7]Xaa1-8, [Cyc4-7]Xaa1-7, [Cyc4-7]Xaa2-7, [Cyc4-7]Xaa2-8 or [Cyc4-7]Xaa3-8, wherein
Xaa1 is Asp Xaa2 is Arg Xaa3 is Ile or Val Xaa5 is Ile or Val Xaa6 is His Xaa8 is Phe or Ile Xaa9 is His Xaa10 is Ile, Val or Leu,and wherein the thioether-bridge linkage between the amino acids corresponding to positions Tyr4 and Pro7 is of the general formula: wherein R, R1, R2, R3, R4 and R5 are independently selected from —H, a lower (e.g. C1-C10) alkyl and aralkyl group.