Structural comparison between type I and type II antagonists: possible implications in the drug design of AT1 antagonists.
Analogues of sarilesin (type I AT1 antagonists), and sarmesin (type II AT1 antagonists) with homoserine (hSer) at position 8 were prepared and bioassayed. The presence of a Tyr4-Ile5-His6 bend found in sarmesin but not in sarilesin was identified. The obtained results coupled with conformational analysis studies, using a combination of NMR spectroscopy and computational chemistry, propose important conformational and stereoelectronic properties for agonist and antagonist activity at AT1 receptors.
Roumelioti
P
P
Department of Chemistry, University of Patras, Greece.
Tselios
T
T
Alexopoulos
K
K
Mavromoustakos
T
T
Kolocouris
A
A
Moore
G J
GJ
Matsoukas
J M
JM
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D015195:Drug Design; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C040420:angiotensin II, Sar(1)-Me-Tyr(4)-; D000803:Angiotensin I