ACTH AND RELATED PEPTIDES

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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.