STTR Phase I: Cloning of the Diterpene Cyclase Involved in Pseudopterosin/Seco-Pseudopterosin Biosynthesis

STTR I 期：克隆参与拟珊瑚素/Seco-拟珊瑚素生物合成的二萜环化酶

• 批准号: 0610626
• 负责人: Lory Santiago-Vazquez
• 金额: $ 10万
• 依托单位: Nautilus Biosciences
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0610626&HistoricalAwards=false
• 关键词: STTR; Phase; Cloning; Diterpene; Cyclase

This Small Business Technology Transfer (STTR) Phase I Project describes the development of a commercially relevant sustainable production method of a family of anti-inflammatory agents, the pseudopterosins. These compounds and the related seco-pseudopterosins are isolated from the gorgonian coral, Pseudopterogorgia elisabethae, and shown to have promising activity in various in vitro and in vivo models. Methopterosin, the methyl ether of pseudopterosin A, has progressed through Phase I and II clinical trials as a topical antiinflammatory agent. Currently, the only source of these compounds is from extractions of biomass collected from reefs. The aim of the work described is to purify and sequence the native terpene synthase involved in the biosynthesis of these compounds and clone the corresponding gene. This would represent the first cloning of a terpene synthase from any marine organism. Marine natural products such as the pseudopterosins and seco-pseudopterosins represent an exciting new source of therapeutic agents. The mechanism of action of the pseudopterosins appears to be novel suggesting that these marine natural products represent a new class of anti-inflammatory drugs with a commercial market as a cosmetic additive and a future clinical market.

这个小企业技术转让（STTR）第一阶段项目描述了一个商业相关的可持续生产方法的抗炎药家族，伪蝶呤的发展。这些化合物和相关的裂-假蝶呤分离自柳珊瑚，Pseudopterogorgia elisabethae，并显示在各种体外和体内模型中具有有希望的活性。甲蝶呤，假蝶呤A的甲基醚，已经通过I期和II期临床试验作为局部麻醉剂取得进展。目前，这些化合物的唯一来源是从珊瑚礁收集的生物质提取物。所描述的工作的目的是纯化和测序参与这些化合物的生物合成的天然萜烯合酶，并克隆相应的基因。 这将代表首次从任何海洋生物中克隆萜烯合酶。海洋天然产物如假蝶呤和开环假蝶呤代表了令人兴奋的治疗剂的新来源。假蝶呤的作用机制似乎是新颖的，这表明这些海洋天然产物代表了一类新的抗炎药物，具有作为化妆品添加剂的商业市场和未来的临床市场。