Receptor binding affinity and thermolysin degradation of truncated and retro-inverso-isomeric ANF analogs
| Autor: | Stephen H. Buck, C. F. Hassman, Berman Judd M, Teng-Man Chen |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
animal structures
Stereochemistry Thermolysin Receptors Cell Surface Muscle Smooth Vascular General Biochemistry Genetics and Molecular Biology Structure-Activity Relationship Hydrolysis Spontaneously hypertensive rat Isomerism Rats Inbred SHR Animals General Pharmacology Toxicology and Pharmaceutics Neprilysin Aorta Cells Cultured chemistry.chemical_classification integumentary system Chemistry Ligand binding assay Cell Membrane General Medicine In vitro Rats Kinetics Enzyme Membrane Biochemistry Receptors Atrial Natriuretic Factor Atrial Natriuretic Factor |
| Zdroj: | Life Sciences. 44:1267-1270 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/0024-3205(89)90363-9 |
| Popis: | The peptides H-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-NH 2 (rANF 8−15 -NH 2 ), Ac-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-NH 2 (Ac-rANF 8−15 -NH 2 ), and their corresponding retro-inverso-isomeric peptides H-D-Ile-D-Arg-D-Asp-D-Ile-D-Arg-Gly-Gly-D-Phe-NH 2 (D-rANF 15−8 -NH 2 ), Ac-D-Ile-D-Arg-D-Asp-D-Ile-D-Arg-Gly-Gly-D-Phe-NH 2 (Ac-D-rANF 15−8 -NH 2 ), were evaluated for their ability to compete for the binding of 125 I-rANF 5−28 to cultured spontaneously hypertensive rat (SHR) aortic smooth muscle cell membranes. Their stability toward hydrolysis by the neutral endopeptidase thermolysin was also studied. The octapeptides rANF 8−15 -NH 2 and Ac-rANF 8−15 -NH 2 bound with IC 50 's of 367 pM and 1900 pM, respectively, but were rapidly hydrolyzed by thermolysin. Retro-inverso-isomers were prepared to provide molecules with an improved enzymatic stability. The retro-inverso-isomers were completely stable to thermolysin but were virtually inactive in the binding assay (IC 50 1 μ M). |
| Databáze: | OpenAIRE |
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