Centre for Biocatalytic Manufacture of New Modalities (CBNM)

新模式生物催化制造中心（CBNM）

• 批准号: EP/S005226/1
• 负责人: Nicholas Turner
• 金额: $ 280.16万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS005226%2F1
• 关键词: Centre; Biocatalytic; Manufacture; New; Modalities

In the ever developing world of pharmaceuticals and treatments of diseases new, more challenging drug targets are being identified that require ever more complex drug molecules. These complex molecules or "New Modalities" bridge the gap between the two existing classes of compounds, small molecules (e.g. Aspirin) and biologics (Antibodies), and are typically larger than the existing small molecules but smaller than traditional biologics. These new classes of molecule offer great promise as novel therapies and indeed many of these medicines are aimed at biological targets that cannot be addressed by traditional either small molecule or antibody derived drugs. The complexity of the new modalities currently results in high cost of manufacture which offers an opportunity to develop lower cost routes to produce these compounds. Small molecule manufacturer has benefited from adopting biocatalysis within manufacturing strategies and has demonstrated the potential for use of these catalysts in wider chemical manufacture, such as reduced waste streams, lower energy costs and reduced costs of goods including solvents. Indeed, the project partners have already generated some early proof-of-concept studies, backed up by a wider literature evidence base suggesting that biocatalysis can be used in the synthesis of these new modalities.Through the partnership of the University of Manchester, AstraZeneca and Prozomix we are bringing together a diverse range of experts that will facilitate the development of new manufacturing strategies to produce these new modalities in an efficient and cleaner manner. The use of biocatalysis has the potential to allow access to chemistries and control of manufacture that are otherwise unavailable to the pharmaceutical manufacturing community. Culminating in lower cost manufacturing that translates into greater access to the next generation of drug for a wider community.

在药物和疾病治疗的不断发展的世界中，新的、更具挑战性的药物靶点正在被确定，这需要更复杂的药物分子。这些复杂分子或“新形态”弥合了两类现有化合物（小分子（例如阿司匹林）和生物制剂（抗体））之间的差距，并且通常大于现有小分子但小于传统生物制剂。这些新的分子类别作为新的疗法提供了巨大的希望，并且实际上这些药物中的许多针对传统的小分子或抗体衍生药物无法解决的生物靶标。目前新模式的复杂性导致高制造成本，这提供了开发较低成本路线以生产这些化合物的机会。小分子制造商从在制造战略中采用生物催化中受益，并已证明这些催化剂在更广泛的化学制造中的潜力，例如减少废物流，降低能源成本和降低包括溶剂在内的商品成本。事实上，项目合作伙伴已经产生了一些早期的概念验证研究，并得到了更广泛的文献证据基础的支持，表明生物催化可以用于这些新模式的合成。通过与曼彻斯特大学的合作，阿斯利康和Prozomix我们汇集了各种各样的专家，将促进新的制造战略的发展，以生产这些新的模式，高效、清洁的方式。生物催化的使用有可能允许获得化学品和控制生产，否则无法获得制药界。最终降低了制造成本，使更广泛的社区更容易获得下一代药物。

项目成果

Biocatalysis

• DOI: 10.1038/s43586-021-00044-z
• 发表时间: 2021-06-24
• 期刊: NATURE REVIEWS METHODS PRIMERS
• 作者: Bell, Elizabeth L.;Finnigan, William;Flitsch, Sabine L.
• 通讯作者: Flitsch, Sabine L.

Characterization of native protein structure with ion mobility mass spectrometry, multiplexed fragmentation strategies and multivariant analysis

• DOI: 10.1016/j.ijms.2021.116588
• 发表时间: 2021-03-26
• 期刊: INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
• 影响因子: 1.8
• 作者: Black, Rachelle;Barkhanskiy, Alexey;Barran, Perdita E.
• 通讯作者: Barran, Perdita E.

Mechanism of Action of Flavin-Dependent Halogenases.

• DOI: 10.1021/acscatal.2c05231
• 发表时间: 2022-12-16
• 期刊: ACS CATALYSIS
• 影响因子: 12.9
• 作者: Barker, Rhys D.;Yu, Yuqi;De Maria, Leonardo;Johannissen, Linus O.;Scrutton, Nigel S.
• 通讯作者: Scrutton, Nigel S.

Biocatalysis in Drug Design: Engineered Reductive Aminases (RedAms) Are Used to Access Chiral Building Blocks with Multiple Stereocenters.

• DOI: 10.1021/jacs.3c07010
• 发表时间: 2023-10-11
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Casamajo, Arnau Rue;Yu, Yuqi;Schnepel, Christian;Morrill, Charlotte;Barker, Rhys;Levy, Colin W.;Finnigan, James;Spelling, Victor;Westerlund, Kristina;Petchey, Mark;Sheppard, Robert J.;Lewis, Richard J.;Falcioni, Francesco;Hayes, Martin A.;Turner, Nicholas J.
• 通讯作者: Turner, Nicholas J.

Ion Mobility Mass Spectrometry (IM-MS) for Structural Biology: Insights Gained by Measuring Mass, Charge, and Collision Cross Section.

• DOI: 10.1021/acs.chemrev.2c00600
• 发表时间: 2023-03-22
• 期刊: CHEMICAL REVIEWS
• 影响因子: 62.1
• 作者: Christofi, Emilia;Barran, Perdita
• 通讯作者: Barran, Perdita