ACTH AND RELATED PEPTIDES

本续期申请的主要目的是研究 促肾上腺皮质激素、促黑素、β-内啡肽 β-促脂素及其相关肽。 具体目标如下： (1)为了分离β-促脂素（β-LPH）、ACTH和β-内啡肽， （β-EP）从马和大象垂体腺，并确定其 氨基酸序列。 (2)合成马、大象和鸵鸟的促肾上腺皮质激素 和β-内啡肽。 以确定原发性 鸵鸟脑垂体β-LPH结构。 研究 马、象的脂解、类固醇生成和免疫活性 和鸵鸟Beta-LPH的生物活性进行比较， 其他物种。 (3)为了确定醛固酮刺激活性， ACTH、α-MSH、β-MSH和β-LPH的各种合成类似物。 到 固相法合成马β-MSH和[Des-Asp1]-β-MSH 并对合成产物的生物活性进行了研究， 促黑素、脂解和类固醇生成效力。 继续 合成ACTH和MSH肽，目的如下：a） 进一步确定激素的那些基本结构特征， B）制备选择性地 抑制ACTH或MSH生物活性，和c）制备ACTH类似物 主要具有皮质酮或醛固酮刺激活性。 到 合成了人异源LPH并研究了其生物活性。 到 建立了人血清中不同浓度LPH的放射免疫分析方法。(4)纯化和 表征膜中β-EP的结合蛋白或受体 从大鼠或/和牛匀浆以及从 神经母细胞瘤X胶质瘤杂交细胞。

The chief objective of this renewal application is to study the structure-activity relationship of ACTH, melanotropins, beta-endorphin, Beta-lipotropin and related peptides. The specific aims are as follows: (1) To isolate Beta-lipotropin, (Beta-LPH), ACTH and beta-endorphin, (Beta-EP) from horse and elephat pituitary glands and to determine their amino acid sequences. (2) To synthesize horse, elephant and ostrich ACTH and Beta-endorphin by the solid-phase method. To determine the primary structure of Beta-LPH from ostrich pituitary glands. To study the lipolytic, steroid-ogenic and immunological activities of horse, elephant and ostrich Beta-LPH and compare their biological activities with that from other species. (3) To determine the aldosterone-stimulating activity of various synthetic analogs of ACTH, Alpha-MSH, Beta-MSH and Beta-LPH. To synthesize horse Beta-MSH and [Des-Asp1]-Beta-MSH by the solid phase method and to study the biological activity of the synthetic products for their melanotropic, lipolytic and steroidogenic potency. To continue the synthesis of ACTH and MSH peptides with the following objectives: a) to further define those structure features of the hormone which are essential for the biological functions; b) to prepare peptides which selectively inhibit biological activity of ACTH or MSH and c) to prepare ACTH analogs with mainly corticosterone - or aldosterone-stimulating activity. To synthesize human varies as-LPH and study its biological activity. To develop radioimmunoassay for human varies as-LPH. (4) To purify and characterize the binding protein or the receptor for Beta-EP in membrane preparation from rat or/and bovine homogenates as well as from neuroblastoma X glioma hybrid cells.