INSECT DIURETIC HORMONES--STRUCTURES AND FUNCTION

昆虫利尿激素——结构和功能

• 批准号: 2185649
• 负责人: DAVID Allan SCHOOLEY
• 金额: $ 15.78万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2185649
• 关键词: Diptera; Hymenoptera; Lepidoptera; bioassay; circular dichroism; computer simulation; conformation; diuresis; enzyme linked immunosorbent assay; hormone receptor; hormone regulation /control mechanism; immunoaffinity chromatography; invertebrate hormone; mass spectrometry; neuropeptide receptor; neuropeptides; nuclear magnetic resonance spectroscopy; protein purification; protein sequence; protein structure function; receptor binding; urination

Insects have low pressure circulatory systems and require diuretic hormones to control production by Malpighian tubules of primary urine. The first insect diuretic hormone (DH) identified (1987) is homologous to arginine vasopressin. The second identified, Manduca sexta DH (1989), is structurally homologous to the corticotropin releasing factor/sauvagine/urotensin I family of neuropeptides. In 1991 several additional insect DHs have been identified, which are homologous to M. sexta DH. An extremely novel aspect of the sequences of the M. sexta DH family of peptides is that they have homologous regions for the amino terminal half of the 41-46 residue sequence, and homology at the carboxyl terminus of the molecule, but gaps are required in the less homologous part of the molecules for good alignment of both termini. These gaps in the sequence should cause profound differences in the three dimensional conformation of the related insect DHs; curiously, the form with the biggest gap in its sequence still has biological activity in Malpighian tubules of the species with the smallest gap in its sequence. We propose studies to isolate and identify additional members of this family of neuropeptides, using an existing enzyme-linked immunosorbent assay to monitor peptide isolations. We also plan to study the relative three dimensional conformation of the members of this family by both computer modeling and by physico-chemical methods (600 MHz NMR and circular dichroism spectrometry on synthetic samples). We will also try to correlate structure with function by studying the relative affinity of the peptides for receptor preparations from two different species of insects, and also study their activity in bioassays. Such studies on this unique family of neuropeptides will provide conformational information which may be of general utility in planning synthesis of neuropeptide analogues. Usually chemical analogue synthesis of neuropeptides is geared to truncations and amino acid substitutions. In addition, it is possible that diuretic peptides may be used in biotechnological approaches for control of mosquitoes and other blood-feeding disease vectors, as very rapid diuresis is essential for survival of blood-feeders. Analogues of insect juvenile hormones (sesquiterpenoids) are currently in commercial use as extremely safe, specific insect control agents.

昆虫有低压循环系统，需要利尿剂 激素来控制初级尿的马氏管的产生。 1987年发现的第一种昆虫利尿激素（DH）与 精氨酸加压素 第二个被鉴定的是Manducasexta DH（1989）， 结构上与促肾上腺皮质激素释放 因子/sauvagine/尾加压素I神经肽家族。 1991年，几 已经鉴定了与M同源的其它昆虫DH。 塞克斯塔DH。 一个非常新颖的方面的序列的M。sexta DH 肽家族的一个重要特征是它们具有氨基酸的同源区域， 41-46个残基序列的末端一半，并且在羧基处同源 分子的末端，但在同源性较低的 分子的一部分，用于两个末端的良好对齐。 这些差距在 这一序列应该会在三维空间中造成深刻的差异， 相关昆虫DH的构象;奇怪的是， 其序列中最大的缺口在马尔皮基氏中仍具有生物活性 在其序列中具有最小间隙的物种的小管。 我们提出 研究分离和鉴定该家族的其他成员， 神经肽，使用现有的酶联免疫吸附测定， 监测肽分离。 我们还计划研究相对的三个 这一家庭的成员的空间构象，由两个计算机 建模和物理化学方法（600 MHz NMR和循环 合成样品上的二色性光谱）。 我们还将努力 通过研究结构与功能的相对亲和力， 用于来自两种不同物种的受体制剂的肽 昆虫，并研究其在生物测定中的活性。 对这一独特的神经肽家族的研究将提供 可能在规划中具有普遍效用的构象信息 神经肽类似物的合成。 通常化学类似物合成 神经肽的功能主要是截短和氨基酸取代。 此外，利尿肽可能用于治疗糖尿病。 采用生物技术方法控制蚊子和其他 血液喂养的疾病载体，因为非常快速的利尿是必不可少的， 吸血鬼的生存 昆虫保幼激素类似物 （倍半萜类化合物）目前在商业上使用是非常安全的， 特定昆虫控制剂。