Bicyclic tripeptide mimetics with reverse turn inducing properties.
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.
Department of Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
P
P
Johannesson
G
G
Lindeberg
W
W
Tong
A
A
Gogoll
A
A
Karlén
A
A
Hallberg
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D017433:Protein Structure, Secondary; D011869:Radioligand Assay; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II