Berman J M, Hassman C F, Buck S H, Chen T M
Merrell Dow Research Institute, Cincinnati, OH 45215.
Life Sci. 1989;44(18):1267-70. doi: 10.1016/0024-3205(89)90363-9.
The peptides H-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-NH2 (rANF8-15-NH2), Ac-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-NH2 (Ac-rANF8-15-NH2), and their corresponding retro-inverso-isomeric peptides H-D-Ile-D-Arg-D-Asp-D-Ile-D-Arg-Gly-Gly-D-Phe-NH2 (D-rANF15-8-NH2), Ac-D-Ile-D-Arg-D-Asp-D-Ile-D-Arg-Gly-Gly-D-Phe-NH2 (Ac-D-rANF15-8-NH2), were evaluated for their ability to compete for the binding of 125I-rANF5-28 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 rANF8-15-NH2 and Ac-rANF8-15-NH2 bound with IC50'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 (IC50 greater than 1 microM).
对肽H-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-NH2（rANF8-15-NH2）、Ac-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-NH2（Ac-rANF8-15-NH2）及其相应的反向异构体肽H-D-Ile-D-Arg-D-Asp-D-Ile-D-Arg-Gly-Gly-D-Phe-NH2（D-rANF15-8-NH2）、Ac-D-Ile-D-Arg-D-Asp-D-Ile-D-Arg-Gly-Gly-D-Phe-NH2（Ac-D-rANF15-8-NH2），评估它们竞争125I-rANF5-28与培养的自发性高血压大鼠（SHR）主动脉平滑肌细胞膜结合的能力。还研究了它们对中性内肽酶嗜热菌蛋白酶水解的稳定性。八肽rANF8-15-NH2和Ac-rANF8-15-NH2的结合IC50分别为367 pM和1900 pM，但被嗜热菌蛋白酶迅速水解。制备反向异构体以提供具有改善的酶稳定性的分子。反向异构体对嗜热菌蛋白酶完全稳定，但在结合试验中几乎无活性（IC50大于1 microM）。
