讲座概要
Natural products have long been regarded as “Nature’s medicine chest” providing invaluable platforms for developing front-line drugs. The chemical structures of natural products have evolved over several millennia for a specific biochemical purpose and their molecular frameworks can be considered “privileged，scaffolds.”The synthesis of several bioactive natural products as “privileged scaffolds” for drug discovery will be described. This lecture will also showcase our research on the synthesis of peptidomimetics,lipopeptides and glycopeptides as a platform for the discovery and development of peptide therapeutics as agents to treat neurogenetic disorders,infectious disease, cancer and diabetes. One example includes the peptidomimetic drug candidate trofinetide (NNZ2566) that was approved by the US FDA in 2023 as the first drug for the treatment of Rett Syndrome (tradename DaybueTM).
天然产物长期以来被视为“大自然的药库”，为开发一线药物提供了宝贵的平台。天然产物的化学结构已经进化了几千年，具有特定的生化目的，其分子框架可被视为“特权支架”。本次讲座将介绍几种生物活性天然产物作为药物发现的“特权支架”的合成方法，将展示本课题组在肽模拟物、脂肽和糖肽合成方面的研究成果，特别是作为发现和开发肽疗法作为治疗神经遗传疾病、传染病、癌症和糖尿病的药物的平台。一个成功案例包括肽模拟物候选药物曲芬肽 (NNZ2566)，它于 2023 年被美国 FDA 批准为治疗雷特综合征的首个药物（商品名 DaybueTM ）
主讲人介绍
Professor Margaret Brimble has long been committed to organic synthesis, natural product synthesis, asymmetric synthesis, carbohydrate chemistry, the synthesis of new generation antibiotics and pesticides and herbicides. Her research focuses on the synthesis of new bioactive natural products/antimicrobial peptides and the synthesis of lipopeptides for cancer vaccines and new biomaterials. As of May 2024, Professor Brimble has published more than 560 papers and 96 reviews in international mainstream chemical journals such as J. Am. Chem. Soc., Angew. Chem. Int. Ed.. And she is the inventor of more than 50 patents.
She discovered the drug DAYBUE™, and also discovered the investigational new drug NNZ2591 for Neuren Pharmaceuticals that is in phase 2 clinical trials for Phelan-McDermid syndrome, Angelman syndrome, Pitt Hopkins syndrome and Prader-Willi syndrome. She is co-founder of the cancer immunotherapy company SapVax.llc that has licensed her CLipPA peptide lipidation technology to develop self-adjuvanting peptide-based cancer vaccines.
Professor Margaret Brimble is an Executive Editor for Organic Letters, Fellow of The Royal Society (FRS)–first female New Zealander (since 2018), Fellow of the Royal Society of New Zealand (FRSNZ) since 2001 and a Dame Companion of the New Zealand Order of Merit (DNZM).
玛格丽特·布林布尔教授长期致力于天然产物全合成、新一代抗生素和疫苗合成、碳水化合物化学研究，特别是新型生物活性天然产物/抗菌肽的合成及其在医药领域中的应用。截止2024年5月，玛格丽特·布林布尔教授在国际顶级化学期刊如J. Am. Chem. Soc., Angew. Chem. Int. Ed.等以通讯作者身份共计发表发表了560多篇论文、96篇评论，授权发明专利50余项。
玛格丽特·布林布尔教授代表性产业化成果是开发了肽类药物“Trofinetide” ，其实验室还发现了独特的神经营养候选药物NNZ-2591，该药物已被证明在另外四种神经发育障碍的临床前模型中取得了积极成果——安吉曼综合征、皮特霍普金斯综合征、菲兰-麦克德米德综合征和普拉德-威利综合征，并且正在进行2期临床试验。她还与他人共同创立了癌症免疫治疗公司SapVax开发基于肽的自辅助癌症疫苗。
玛格丽特·布林布尔教授是化学一区期刊Organic Letters执行主编、2018年当选英国皇家学会院士（新西兰第一位获此殊荣的女性科学家）、新西兰皇家科学院院士（2001年当选），新西兰功绩勋章获得者（女爵）。
( 图文/Margaret Brimble、编辑/刘怡宁、初审/蒙晨、复审/赖凯声、终审/汪勇)
