Abstract
Analogues of the hypertensive octapeptide angiotensin II, comprising novel constrained 5,8-bicyclic and 5,9-bicyclic tripeptide units adopting nonclassical beta-turn geometries, as deduced from theoretical conformational analysis, have been synthesized. Spontanous bicyclization upon acid-catalyzed deprotection of a model peptide, encompassing a protected omega-formyl alpha-amino acid in position 5 and cysteine residues in positions 3 and 7, revealed a strong preference for bicyclization toward the C-terminus. The bicyclic thiazolidine related angiotensin II analogues synthesized exhibited no affinity for the angiotensin II AT1 receptor.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Angiotensin II / analogs & derivatives*
-
Angiotensin II / chemical synthesis*
-
Angiotensin II / chemistry
-
Angiotensin II / metabolism
-
Animals
-
CHO Cells
-
Cricetinae
-
In Vitro Techniques
-
Liver / metabolism
-
Magnetic Resonance Spectroscopy
-
Models, Molecular
-
Molecular Mimicry
-
Protein Structure, Secondary
-
Radioligand Assay
-
Rats
-
Receptor, Angiotensin, Type 1
-
Receptor, Angiotensin, Type 2
-
Receptors, Angiotensin / metabolism
-
Vasoconstrictor Agents / chemical synthesis*
-
Vasoconstrictor Agents / chemistry
-
Vasoconstrictor Agents / metabolism
Substances
-
Receptor, Angiotensin, Type 1
-
Receptor, Angiotensin, Type 2
-
Receptors, Angiotensin
-
Vasoconstrictor Agents
-
Angiotensin II