Development of Novel Bioprocess Platform for Rapid, Economical Production of Pept

开发用于快速、经济生产肽的新型生物工艺平台

• 批准号: 7325568
• 负责人: APRILE L PILON
• 金额: $ 16.95万
• 依托单位: APC BIOTECHNOLOGY SERVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-04 至 2008-05-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7325568
• 关键词: Address; Affect; Affinity Chromatography; Amines; Amino Acids; Antifungal Agents; B-insulin; Bacteria; Binding; Biological Products; Biomedical Research; C-terminal; CCL26 gene; Charge; Chemicals; Chimeric Proteins; Chitin; Chromatography; Cleaved cell; Communities; Complex; Condition; Copper; DNA Sequence; Development; Diabetes Mellitus; Disulfides; Endopeptidases; Epidemic; Escherichia coli; Generic Drugs; Genes; Government; Guanosine Monophosphate; High Pressure Liquid Chromatography; Human; Industry; Insulin; Kilogram; Length; Metals; Methods; Molecular Conformation; Mycoses; N-terminal; Nature; Numbers; Object Attachment; Pain Research; Peptide Hydrolases; Peptide Library; Peptide Synthesis; Peptides; Phase; Preparation; Process; Production; Protease Gene; Proteins; Proteolysis; Proteolytic Processing; Range; Reaction; Research; Research Personnel; Sepharose; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solid; Solutions; Speed; Standards of Weights and Measures; Structure; System; Techniques; Testing; Time; Vaccines; Validation; Work; bacterial lysate; base; biodefense; bioprocess; chemical standard; chemical synthesis; concept; cost; density; design; design and construction; disulfide bond; expression cloning; expression vector; gene cloning; imidazole-4-acetic acid; interest; magnetic beads; milligram; novel; oxidation; peptide B; protein aminoacid sequence; protein expression; protein structure; reaction rate; recombinant peptide; scale up; size; tool

DESCRIPTION (provided by applicant): A novel bioprocess platform, involving synthesis of peptide and protein biopharmaceutical products as fusions with a synthetic "anchor" protein in bacteria, and subsequent proteolytic cleavage, will be developed. The unique features of the system allow for the economical production of large quantities of simple linear peptides, as well as complex, multi-component peptides. Proof of concept will be demonstrated by synthesizing three peptides of varying sizes; a 12-mer anti-fungal peptide, a 40-mer psalmotoxin, and an 86-mer, pro-insulin. Preliminary studies and cost projections suggest that peptides ranging from about 8 to 100 amino acids can be produced for a few dollars per gram, in contrast to chemical synthetic methods for which costs dramatically increase with the length of the peptide product. Another major advantage is the rapidity with which each product can be generated and the generic nature of the process for many peptide and protein products, facilitating scale-up. Additionally, the three peptide products have their own inherent commercial value. A more efficient bioprocess for human insulin can help meet growing demand. Diabetes is a growing worldwide epidemic that is particularly severe in the U.S and a more efficient bioprocess for human insulin would be immediately useful. This novel, rapid, economical, GMP- enabled bioprocess platform for recombinant peptides and proteins can help meet production requirements, at all levels of production from research quantities to kilograms, in the biopharmaceutical, vaccine, biodefense, and biomedical research industries. The economy and speed with which novel peptides and proteins may be produced from a UBL-type expression system and solid matrix UBL protease fill a great need in industry and could also address some of the government's biodefense requirements for very rapid production of large quantities of vaccines and biopharmaceuticals. Kits for production of peptide libraries based on the UBL expression system could also be of significant value to the biomedical research community. To develop this system and demonstrate its potential, we will synthesize three peptides, each of commercial interest, including human insulin for treatment of diabetes, psalmatoxin peptide for pain research, and MUC7 peptide for treatment of fungal infections.

描述（由申请人提供）：将开发一个新的生物工艺平台，包括肽和蛋白质生物制药产品的合成，作为与细菌中合成的“锚”蛋白的融合，以及随后的蛋白水解裂解。该系统的独特功能允许经济生产大量简单的线性肽，以及复杂的多组分肽。概念的证明将通过合成三种不同大小的肽来证明；12个分子的抗真菌肽，40个分子的草毒素，86个分子的胰岛素原。初步研究和成本预测表明，生产8到100个氨基酸的肽每克只需几美元，而化学合成方法的成本则随着肽产品的长度而急剧增加。另一个主要优点是每个产品都可以快速生成，并且许多肽和蛋白质产品的过程具有通用性质，便于扩大规模。此外，这三种肽产品具有各自内在的商业价值。一种更有效的人胰岛素生物工艺可以帮助满足日益增长的需求。糖尿病是一种日益严重的世界性流行病，在美国尤为严重，而一种更有效的人类胰岛素生物工艺将立即发挥作用。这个新颖、快速、经济、符合GMP的重组肽和蛋白质的生物工艺平台可以帮助满足生物制药、疫苗、生物防御和生物医学研究行业从研究数量到公斤的所有生产水平的生产要求。从UBL型表达系统和固体基质UBL蛋白酶中生产新型多肽和蛋白质的经济和速度填补了工业上的巨大需求，也可以解决政府对快速生产大量疫苗和生物制药的一些生物防御要求。基于UBL表达系统的肽库生产试剂盒对生物医学研究界也具有重要价值。为了开发这一系统并展示其潜力，我们将合成三种具有商业价值的肽，包括用于治疗糖尿病的人胰岛素，用于疼痛研究的psalmatoxin肽和用于治疗真菌感染的MUC7肽。