New approaches for the site-selective chemical modification of therapeutic proteins under mild conditions
在温和条件下对治疗性蛋白质进行位点选择性化学修饰的新方法
基本信息
- 批准号:223529902
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Priority Programmes
- 财政年份:2012
- 资助国家:德国
- 起止时间:2011-12-31 至 2018-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The site-specific chemical modification of protein therapeutics, for example antibodies, protein hormones, and cytokines, is of great importance for applications in cancer and disease treatment, diagnostics, and imaging. Chemical modifications can endow the protein therapeutics with new and tailored properties, for example longer circulation time in the blood-stream, targeted cell-killing (immunoconjugates), and reporting their localization (e.g. by fluorophores or tracers). In this project, we explore protein trans-splicing catalyzed by split inteins. Split inteins ligate their fused peptide or protein sequences with a native peptide bond and concomitantly remove themselves during the reaction, thus making the approach virtually traceless. We have developed and continue to improve two types of approaches to use protein trans-splicing for the preparation of chemically modified proteins. The synthetic moiety is transferred to the target protein either by splicing of a synthetic peptide with a recombinant protein (semi-synthetic protein trans-splicing) or by splicing of a short tag prelabeled at a unique cysteine or unnatural amino acid residue (chemical-tag splicing). In the second funding period we will generate new functional, chemically modified proteins and analyze them for biochemical and biomedical properties. The focus will be on antibody fragments potentially useful as protein therapeutics and for cellular imaging. We will also continue to develop new split-intein based technologies for selective chemical modification of proteins under mild and native conditions. These protein chemical tools are expected to be of high interest for a broad range of applications.
蛋白质治疗的位点特异性化学修饰,例如抗体、蛋白质激素和细胞因子,在癌症和疾病治疗、诊断和成像方面的应用非常重要。化学修饰可以赋予蛋白质疗法新的和定制的特性,例如更长的血液循环时间,靶向细胞杀伤(免疫偶联物),并报告其定位(例如通过荧光团或示踪剂)。在这个项目中,我们探索了由分裂内链催化的蛋白质反式剪接。分裂内链将其融合的肽或蛋白质序列与天然肽键连接,并在反应过程中同时去除自己,从而使该方法几乎无迹可寻。我们已经开发并继续改进两种方法来使用蛋白质反式剪接来制备化学修饰的蛋白质。合成片段通过与重组蛋白的合成肽剪接(半合成蛋白反式剪接)或通过在独特的半胱氨酸或非天然氨基酸残基上预标记的短标签剪接(化学标签剪接)转移到目标蛋白上。在第二个资助期,我们将生成新的功能,化学修饰的蛋白质,并分析它们的生化和生物医学特性。重点将放在抗体片段上,作为蛋白质治疗和细胞成像的潜在用途。我们还将继续开发基于分裂蛋白的新技术,在温和和自然条件下对蛋白质进行选择性化学修饰。这些蛋白质化学工具有望具有广泛的应用价值。
项目成果
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会议论文数量(0)
专利数量(0)
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Professor Dr. Henning D. Mootz其他文献
Professor Dr. Henning D. Mootz的其他文献
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{{ truncateString('Professor Dr. Henning D. Mootz', 18)}}的其他基金
Development and optimization of photo-switchable inteins for the control of antibodies by light
用于通过光控制抗体的光可切换内含肽的开发和优化
- 批准号:
411621994 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Research Grants
Mechanistic Studies and Directed Protein Evolution of a Semi-synthetic Intein
半合成内含肽的机理研究和定向蛋白质进化
- 批准号:
116694402 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Research Grants
Präparation semi-synthetischer Proteine durch ein neuartiges trans-spleißendes Intein
使用新型反式剪接内含肽制备半合成蛋白质
- 批准号:
22175865 - 财政年份:2006
- 资助金额:
-- - 项目类别:
Research Units
Chemical modification of proteins in vivo and generation of switchable proteins by new approaches in semi-synthetic protein chemistry
通过半合成蛋白质化学新方法对体内蛋白质进行化学修饰并生成可转换蛋白质
- 批准号:
5416012 - 财政年份:2003
- 资助金额:
-- - 项目类别:
Independent Junior Research Groups
Nonribosomal peptide synthetases (NRPSs): Understanding functional domain interplay and biosynthetic directionality using FRET spectroscopy
非核糖体肽合成酶 (NRPS):使用 FRET 光谱了解功能域相互作用和生物合成方向性
- 批准号:
434700456 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
Biochemical and structural analysis of unusual docking domains in non-ribosomal peptide synthetases (NRPS)
非核糖体肽合成酶 (NRPS) 中异常对接域的生化和结构分析
- 批准号:
368772725 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
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