INSECT DIURETIC HORMONES--STRUCTURES AND FUNCTION

昆虫利尿激素——结构和功能

• 批准号: 3307653
• 负责人: DAVID Allan SCHOOLEY
• 金额: $ 19.1万
• 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/3307653
• 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。 控制初级尿液马氏管产生的激素。 首次发现的昆虫利尿激素(DH)(1987)与 精氨酸加压素。第二个鉴定为Manduca sexta Dh(1989)，是 在结构上与促肾上腺皮质激素释放同源 因子/苏维素/尾加压素I家族神经肽。1991年，有几个 还鉴定了其他昆虫DHS，它们与M. Sexta DH.六分枝杆菌DNA序列的一个非常新颖的方面 多肽家族的一个特点是它们具有与氨基同源的区域 41-46残基序列的末端一半，以及在羧基上的同源性 分子的末端，但在同源性较低的分子中需要间隙 分子的一部分，使两个末端都能很好地排列。这些差距存在于 这个序列应该会在三维空间中造成深刻的差异 相关昆虫DHS的构象；奇怪的是，与 ITS序列中最大的缺口在马尔皮吉亚仍然具有生物活性 ITS序列中间隙最小的物种的小管。我们建议 分离和鉴定这一家族的其他成员的研究 神经肽，使用现有的酶联免疫吸附试验 监测多肽分离。我们还计划研究相关的三个 用两台计算机研究该家族成员的空间构象 建模和物理化学方法(600 MHz核磁共振和循环 合成样品的二向色性光谱)。我们还将努力 通过研究分子的相对亲和力，将结构与功能联系起来 两种不同物种的受体制剂的多肽 昆虫，并研究它们在生物检测中的活动。 对这一独特的神经肽家族的研究将提供 在规划中可能具有普遍用途的构象信息 神经肽类似物的合成。通常是化学类似物合成 神经肽的主要成分是截断和氨基酸替代。 此外，利尿性多肽可能用于 控制蚊子和其他疾病的生物技术方法 血液传播疾病媒介，因为快速利尿对 食血者的生存。昆虫保幼激素类似物 (倍半萜)目前在商业上使用是极其安全的， 特定的昆虫防治剂。