Goghari M H, DeLean A, Garcia R, Cantin M, Schiller P W
Clinical Research Institute of Montreal, Quebec, Canada.
Int J Pept Protein Res. 1990 Aug;36(2):156-60. doi: 10.1111/j.1399-3011.1990.tb00959.x.
Several analogs of the atrial natriuretic factor (ANF) were synthesized by the solid-phase method using the acetamidomethyl (Acm) group for sulfhydryl protection. The compounds were tested in a receptor binding assay using bovine adrenal zona glomerulosa cell membranes and in the rat diuresis/natriuresis assay. Substitution of tyrosine in position 116 of ANF(101-126) and of the analog [3-Mpr105]ANF(105-126)(3-Mpr = 3-mercaptopropionic acid) did not alter the biological activity profiles and, therefore, these two analogs in radioiodinated form will be useful for enzymatic degradation and clearance studies. Replacement of 3-mercaptopropionic acid with 2-mercaptopropionic acid in [3-Mpr105]ANF(105-126) resulted in an analog with very low potency in both assay systems, presumably as a consequence of the steric bulk and/or local conformational restriction produced by the methyl group attached to the alpha-carbon in position 105. The analog [3-Mpr105,Nva109]ANF(105-126)(Nva = norvaline) showed very low affinity in the receptor binding assay but displayed considerable diuretic/natriuretic activity. The obtained biological activity profiles suggest that in comparison with other ANF peptides the des-amino ANF(105-126) analogs may have a somewhat longer half-life in vivo, or alternatively, may indicate a more complex situation of ANF receptor or binding site heterogeneity.
使用乙酰氨基甲基（Acm）基团进行巯基保护，通过固相法合成了几种心房利钠因子（ANF）类似物。在使用牛肾上腺球状带细胞膜的受体结合试验以及大鼠利尿/利钠试验中对这些化合物进行了测试。在ANF(101 - 126)的116位酪氨酸以及类似物[3 - Mpr105]ANF(105 - 126)（3 - Mpr = 3 - 巯基丙酸）中进行取代，并未改变生物活性谱，因此，这两种放射性碘化形式的类似物将可用于酶促降解和清除研究。在[3 - Mpr105]ANF(105 - 126)中用2 - 巯基丙酸取代3 - 巯基丙酸，得到的类似物在两种试验系统中的活性都非常低，这可能是由于105位α - 碳上连接的甲基产生的空间位阻和/或局部构象限制所致。类似物[3 - Mpr105,Nva109]ANF(105 - 126)（Nva = 正缬氨酸）在受体结合试验中显示出非常低的亲和力，但具有相当大的利尿/利钠活性。所获得的生物活性谱表明，与其他ANF肽相比，去氨基ANF(105 - 126)类似物在体内可能具有稍长的半衰期，或者可能表明ANF受体或结合位点异质性的情况更为复杂。
