VIP FAMILY PEPTIDES-ANALOGS-GH, INSULIN, GLUCAGON

血管活性肠肽（VIP），胰泌素，胰高血糖素，胃抑制 肽（GIP）和最近的PHI和生长激素释放因子 (GRF)是已知能控制 大量胃肠道、胰腺和内分泌事件。 尽管他们的多样性 生物活性，相当大的序列同源性之间存在的每一个 因此创造了一个独特的机会，用于有效的（即值得的 对一种肽的修饰可能被合理地预期直接 适用于另一个序列的可比序列区域）结构-活性 研究旨在检查导致特定生物学的因素， 反应，增加选择性，增加活动， 竞争对手。 这种广泛的SAR研究的肽， 尺寸（ca. 30个残留物）通过我们多年的开发成为可能 七年快速固相合成和HPLC纯化 这些肽中的每一种的技术。 类似地制备的类似物具有 已经产生了更活跃的胰高血糖素和GRF形式，这些设计 战略现在将用于VIP和系列的其他成员。 这些肽的类似物可以预期具有治疗意义 在许多领域，特别是糖尿病，通过阐明新的 控制胰岛素和胰高血糖素水平的机制， 胰高血糖素拮抗剂，通过促胰液素对碳酸氢盐的影响而导致溃疡 释放，通过VIP刺激的支气管扩张引起的某些肺部疾病，以及 在下丘脑GRF缺陷的情况下的生长刺激。 此外，委员会认为， 这些肽的竞争性拮抗剂，以及具有临床 在某些情况下，潜在的，将是非常有价值的阐明 内源性肽的作用机制。 使用的测定方法 这项研究包括对生长激素、催乳素、胰岛素和胰高血糖素的影响 大鼠垂体单层细胞释放GH和催乳素 培养，并在体外对许多组织中腺苷酸环化酶活性的影响 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.