A frame shifted disulfide bridged analogue of angiotensin II.
N-(2-Mercaptoethyl)glycine [NMGly] was incorporated into the 3 and 5 positions of angiotensin II and oxidized to give the corresponding cyclized disulfide c[NMGly(3,5)]Ang II. The binding affinity to the angiotensin II receptor (AT(1)) of this conformationally constrained analogue, which is related to the potent Ang II agonist c[Hcy(3,5)]Ang II, was examined. The analogue had no affinity to the AT(1) receptor. Theoretical conformational analysis was performed to compare the conformational characteristics of model compounds of c[Hcy(3,5)]Ang II and the frame shifted analogue c[NMGly(3,5)]Ang II in an attempt to explain the lack of affinity.
Schmidt
Boris
B
TU Darmstadt, Institut for Organic Chemistry, Petersenstr. 22, D-64287 Darmstadt, Germany. schimbo@oc.chemie.tu.darmstadt.de
Kühn
Christian
C
Ehlert
Dennis K
DK
Lindeberg
Gunnar
G
Lindman
Susanna
S
Karlén
Anders
A
Hallberg
Anders
A
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D004220:Disulfides / Q000737:chemistry*; D007202:Indicators and Reagents; D010455:Peptides / Q000138:chemical synthesis; D011487:Protein Conformation; D011869:Radioligand Assay; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism
D004220:Disulfides; D007202:Indicators and Reagents; D010455:Peptides; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II