Adrenomedullin is a biologically active peptide with multiple functions. Here, we have developed a novel human serum albumin-adrenomedullin (HSA-AM) conjugate, which was synthesized by the covalent attachment of a maleimide derivative of adrenomedullin to the 34^th cysteine residue of human serum albumin via a linker. Denaturing gel electrophoresis and Western blotting for HSA-AM yielded a single band with adrenomedullin immunoreactivity at the position corresponding to a molecular weight (MW) of 73 kDa. Following gel-filtration chromatography, the purified HSA-AM showed a single main peak corresponding with a MW of 73 kDa, indicating that HSA-AM is a monomer. Both adrenomedullin and HSA-AM stimulated the intracellular accumulation of cyclic AMP in HEK-293 cells stably expressing the adrenomedullin 1 receptor. The pEC₅₀ values for adrenomedullin and HSA-AM were 8.660 and 7.208 (equivalent to 2.19 nM and 61.9 nM as EC₅₀), respectively. The bioavailability of HSA-AM compared with that of adrenomedullin was much improved after subcutaneous administration in the rat, which was probably due to the superior resistance of HSA-AM toward endogenous proteases and its reduced clearance from the blood. HSA-AM may be a promising drug candidate for clinical application.

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新型人肾上腺髓质素衍生物的开发：人血清白蛋白偶联的肾上腺髓质素

肾上腺髓质素是一种具有多种功能的生物活性肽。在这里，我们已经开发出一种新的人血清白蛋白的肾上腺髓质素（HSA-AM）缀合物，其通过肾上腺髓质素的马来酰亚胺衍生物的共价连接合成的34^个通过接头的人血清白蛋白的半胱氨酸残基。HSA-AM 的变性凝胶电泳和蛋白质印迹在对应于 73 kDa 的分子量 (MW) 的位置产生了具有肾上腺髓质素免疫反应性的单条带。凝胶过滤层析后，纯化的 HSA-AM 显示一个主峰，对应于 73 kDa 的 MW，表明 HSA-AM 是单体。肾上腺髓质素和 HSA-AM 都刺激了稳定表达肾上腺髓质素 1 受体的 HEK-293 细胞中环 AMP 的细胞内积累。肾上腺髓质素和 HSA-AM的 pEC ₅₀值为 8.660 和 7.208（相当于 EC _{50 的}2.19 nM 和 61.9 nM）， 分别。与肾上腺髓质素相比，HSA-AM 的生物利用度在大鼠皮下给药后显着提高，这可能是由于 HSA-AM 对内源性蛋白酶的优异抵抗力及其从血液中的清除率降低所致。HSA-AM 可能是一种有前景的临床应用候选药物。