Abstract
A benzodiazepine-based beta-turn mimetic has been designed, synthesized, and incorporated into angiotensin II. Comparison of the mimetic with beta-turns in crystallized proteins showed that it most closely resembles a type II beta-turn. The compounds exhibited high to moderate binding affinity for the AT2 receptor, and one also displayed high affinity for the AT1 receptor. Molecular modeling showed that the high-affinity compounds could be incorporated into a previously derived model of AT2 receptor ligands.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin II / chemistry*
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Animals
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Aorta, Thoracic / drug effects
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Aorta, Thoracic / physiology
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Benzodiazepines / chemical synthesis*
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Benzodiazepines / chemistry
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Benzodiazepines / pharmacology
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Drug Design
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Female
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In Vitro Techniques
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Ligands
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Liver / drug effects
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Liver / metabolism
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Models, Molecular
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Molecular Mimicry
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / physiology
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Peptides / chemistry*
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Protein Structure, Secondary
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Rabbits
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Radioligand Assay
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Rats
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Receptor, Angiotensin, Type 1 / agonists*
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Receptor, Angiotensin, Type 1 / metabolism
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Receptor, Angiotensin, Type 2 / agonists*
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Receptor, Angiotensin, Type 2 / metabolism
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Swine
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Uterus / drug effects
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Uterus / metabolism
Substances
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Ligands
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Peptides
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Receptor, Angiotensin, Type 1
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Receptor, Angiotensin, Type 2
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Angiotensin II
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Benzodiazepines