VIP FAMILY PEPTIDES-ANALOGS-GH, INSULIN, GLUCAGON

血管活性肠肽（VIP），促胰液素，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）是一个家族成员， 已知控制许多GI、胰腺和胃肠道的肽， 内分泌事件 尽管它们的生物活性多种多样， 每种肽之间存在相当大的序列同源性， 创造一个独特的机会，有效（即值得 对一种肽的修饰可能被合理地预期为 直接适用于另一个的可比较序列区域） 结构-活性研究旨在阐明 动作，增加活动，发展短，构象 限制类似物，增加选择性，并开发 竞争对手。 如此广泛的肽类SAR研究 这种大小（约30个残基）已成为可能，我们的 经过7年的快速固相反应， 这些化合物的合成和HPLC纯化技术 缩氨酸 类似的类比已经产生了更多的结果。 胰高血糖素和GRF的活性形式以及胰高血糖素和GRF的竞争性拮抗剂， VIP和GRF。 可以预期这些肽的类似物 在许多领域具有治疗意义，尤其是糖尿病 通过阐明新的机制， 控制胰岛素和胰高血糖素水平以及胰高血糖素和GRF 拮抗剂，溃疡通过促胰液素对碳酸氢盐释放的影响， VIP刺激的支气管扩张导致的某些肺部疾病，以及 在下丘脑GRF缺陷的情况下的生长刺激。 此外，所有这些肽的竞争性拮抗剂，如 以及在某些情况下具有临床潜力， 在阐明内源性药物的作用机制方面具有重要价值 缩氨酸 本研究中使用的测定方法包括 对大鼠GH、催乳素、胰岛素和胰高血糖素释放的影响， 单层垂体细胞培养物中GH和催乳素的释放， 以及对组织中腺苷酸环化酶活性的体外影响 类型 后一项研究是与吉恩博士合作进行的。 克里斯多夫 其他正式合作，以评价目前的 和未来的VIP拮抗剂与各种调查和500兆赫 布鲁塞尔的货车宾斯特教授的核磁共振研究已经被 确立了习

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 of 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 elucidating mechanisms of action, increasing activities, developing short, conformationally restricted analogues, increasing selectivities, 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. Analogues prepared similarly have already yielded more active forms of glucagon and GRF and competitive antagonists of VIP and GRF. Analogues 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 and GRF antagonist, ulcers through secretin effect on bicarbonate release, certain lung disorders through VIP-stimulated bronchodilation, and growth stimulation in cases of hypothalamic GRF deficiencies. Furthermore, competitive antagonists of all 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 may tissue types. These latter studies are in collaboration with Dr. Jean Christophe. Other formal collaborations for evaluation of present and future VIP antagonists with various investigators and 500 mhz NMR studies with Professor Van Binst in Brussels have been established.