New Actinomycetes & Other Gram-Positive Marine Bacteria

新放线菌

• 批准号: 6924488
• 负责人: William Fenical
• 金额: $ 27.11万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6924488
• 关键词: Actinomycetales; antineoplastics; aquatic organism; biological products; biomedical equipment development; biotechnology; cooperative study; drug discovery /isolation; gram positive bacteria; liquid chromatography mass spectrometry; microorganism culture; microorganism resource /registry; miniature biomedical equipment; neoplasm /cancer chemotherapy; nuclear magnetic resonance spectroscopy; saltwater environment; sample collection; sedimentation

This is a new research component of the Crews-Novartis NCDDG Program focused on developing new and unique marine bacterial resources from which to derive new drugs for the treatment for cancer. Specific goals include the following: 1. To design and perfect the implementation of new miniaturized sampling devices to access deep-sea sediment samples in replicate numbers to depths of 5000 meters. These samples will be shared with our collaborators as part of the NCDDG Group's annual collecting expeditions. 2. To focus laboratory activities on the isolation of chemically-rich Gram-positive marine bacteria, concentrating on two main groups, the high G+C Gram-positives in the Order Actinomycetales and the low G+C Gram-positives in the Phylum Firmicutes, and to prescreen cultures for their chemical novelty by LCMS analysis. 4. To cultivate in excess of 500, "chemically-novel" (by chemical prescreening), Gram-positive bacteria per year, to adsorbent extract and fractionate these cultures, and to generate "peak libraries" in 96-deep well plate formats, at standardized concentrations (2.5 mg / well) for bioassay at Novartis. 5. By refering to the "active wells", to structurally define the active compound(s) using combined spectral and chemical approaches, including structure modification and the application of mass spectrometry, one- and two-dimensional NMR techniques, and other spectral and chemical methods. 6. To support the Novartis preclinical development program by large-scale cultivation (up to 200 liters) of the active strains, and by isolation and purification of the active compounds in milligram to gram quantities.

这是Crews-Novartis NCDDG计划的新研究组成部分，旨在开发新的和独特的海洋细菌资源，从中为癌症提供新药物。具体目标包括以下内容： 1。设计和完善新的微型采样设备的实施，以访问以5000米深度的重复数字的深海沉积物样品。这些样本将与我们的合作者共享，作为NCDDG集团年度收集探险的一部分。 2。将实验室活动集中在化学丰富的革兰氏阳性海洋细菌的分离上 集中在两个主要组上，分别是放线菌的高g+c革兰氏酶，以及在粉状粉中的低g+c革兰氏酶依赖性，并通过LCMS分析来预先培养其化学新颖性。 4。要种植超过500个，“化学 - 新颖的”（通过化学预筛查），每年革兰氏阳性细菌，吸附提取物和分馏，并在NotArtis的标准化浓度（2.5 mg / well）中以96深板板格式产生“峰值库”。 5。通过参考“活跃井”，使用组合的光谱和化学方法在结构上定义活性化合物，包括结构修饰以及质谱，一维NMR技术以及其他光谱和其他光谱和化学方法的应用。 6。通过大规模培养（多达200升）的活性菌株以及通过毫克中的活性化合物隔离和纯化，以毫克的含量为单位，以支持诺华临床前开发计划。