VIP FAMILY PEPTIDES-ANALOGS-GH, INSULIN, GLUCAGON

血管活性肠肽、促胰液素、胰高血糖素、胃抑制 多肽(GIP)，以及最近的PHI和生长激素释放因子 (GRF)是已知可控制的多肽家族成员 许多胃肠道、胰腺和内分泌事件。尽管他们有不同的 生物活性，它们之间存在着相当大的序列同源性 从而为高效(即有价值)创造了一个独特的机会 对一种多肽的修饰可能合理地被认为是直接 适用于另一个的可比序列区域)结构-活性 旨在检查导致特定生物的因素的研究 回应，增加选择性，增加活动，并发展 竞争对手。对这一多肽进行了如此广泛的SAR研究 大小(约30个残留物)是通过我们在一年多的时间里开发出来的 七年的快速固相合成和高效液相纯化 这些多肽中的每一个的技术。制备的类似物具有类似的 已经产生了更多活性形式的胰高血糖素和GRF，这些设计 战略现在将用于VIP和该系列的其他成员。 这些多肽的类似物有望具有治疗意义。 在许多领域，特别是糖尿病通过阐明新的 控制胰岛素和胰升糖素水平的机制和 胰高血糖素拮抗剂，通过促胰液素对碳酸氢盐的溃疡作用 通过VIP刺激的支气管扩张释放某些肺部疾病，以及 下丘脑GRF缺陷病例的生长刺激。此外， 这些多肽的竞争性拮抗剂，以及临床 在某些情况下，潜势对于阐明 内源性多肽的作用机制。用于以下项目的化验方法 这项研究包括对生长激素、催乳素、胰岛素和胰升糖素的影响。 大鼠体内释放GH和单层垂体腺细胞释放催乳素 培养，以及体外对许多组织中腺苷环化酶活性的影响 类型。

Vasoactive intestinal peptide (VIP), secretin, glucagon, gastric inhibitory peptide (GIP) and, most recently, PHI and growth hormone releasing factor (GRF) are members of a family of peptides which are known to control numerous GI, pancreatic, and endocrine events. Despite their diverse biological activities, considerable sequence homology exists between each peptide thus creating a unique opportunity for efficient (i.e. worthwhile modifications to one peptide might be reasonably expected to be directly applicable to a comparable sequence region of another) structure-activity studies aimed at examining factors responsible for particular biological responses, increasing selectivities, increasing activities, and developing competitive antagonists. Such extensive SAR studies on peptides of this size (ca. 30 residues) have been made possible by our development over a seven year period of rapid solid-phase syntheses and HPLC purification techniques for each of these peptides. Analogs prepared similarly have already yielded more active forms of glucagon and GRF and these design strategies will now be used for VIP and other members of the series. Analogs of these peptides can be expected to have therapeutic significance in many areas, notably diabetes mellitus through the elucidation of new mechanisms governing the control of insulin and glucagon levels and glucagon antagonists, ulcers through secretin effects on bicarbonate release, certain lung disorders through VIP-stimulated bronchodilation, and growth stimulation in cases of hypothalamic GRF deficiencies. Furthermore, competitive antagonists of these peptides, as well as having clinical potentials in some instances, would be of great value in elucidating mechanisms of action of endogenous peptides. Assay methods to be used in this research include effects on GH, prolactin, insulin, and glucagon release in the rat, GH and prolactin release from monolayer pituitary cell cultures, and in vitro effects on adenylate cyclase activity in many tissue types.