VIP FAMILY PEPTIDES-ANALOGS-GH, INSULIN, GLUCAGON

血管活性肠肽、促胰液素、胰高血糖素、胃 抑制肽(GIP)和最近的PHI与生长 激素释放因子(GRF)是一类 已知可控制多种胃肠道、胰腺和 内分泌事件。尽管它们的生物学活动多种多样， 每种多肽之间存在相当大的序列同源性，因此 创造一个独特的高效(即有价值)的机会 对一种多肽的修饰可以合理地预期为 直接适用于另一个的可比序列区域) 旨在阐明其作用机制的构效关系研究 行动，增加活动，发展短期，构象 限制类似物，增加选择性，并发展 竞争对手。如此广泛的多肽合成孔径雷达研究 这种大小(CA.30残基)是由我们的 经过七年的快速固相开发 这些化合物的合成及高效液相色谱纯化技术 多肽。同样制备的类似物已经产生了更多的 胰高血糖素和GRF的活性形式及其竞争性拮抗剂 VIP和GRF。这些多肽的类似物可以预期 在许多领域都有治疗意义，特别是糖尿病 通过阐明控制疾病的新机制 胰岛素、胰高血糖素及GRF的控制 拮抗剂，通过促胰液素作用释放重碳酸盐， 通过VIP刺激的支气管扩张引起的某些肺部疾病，以及 下丘脑GRF缺陷病例的生长刺激。 此外，所有这些肽的竞争性拮抗剂，如 在某些情况下具有临床潜力， 对阐明内源激素的作用机制具有重要价值 多肽。本研究中使用的检测方法包括 对大鼠生长激素、催乳素、胰岛素和胰升糖素释放的影响 单层培养的垂体细胞释放GH和催乳素， 以及体外对梅组织腺苷环化酶活性的影响 类型。后一项研究是与Jean博士合作进行的 克里斯多夫。评估Present的其他正式合作 和未来的VIP拮抗者与各种调查人员和500 MHz 在布鲁塞尔与范·宾斯特教授进行的核磁共振研究 已经成立了。

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.