SBIR Phase I: De Novo Design of Unnatural Peptides - Affordable Drug Discovery Platform

SBIR 第一阶段：非天然肽的从头设计 - 经济实惠的药物发现平台

• 批准号: 1013428
• 负责人: Przemyslaw Czyryca
• 金额: $ 15万
• 依托单位: Allosterix Pharmaceuticals, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1013428&HistoricalAwards=false
• 关键词: SBIR; Phase; De; Novo; Design

This Small Business Innovation Research (SBIR) Phase I project involves testing and validation of a novel drug discovery platform. An original algorithm is used to design previously unknown peptides that are capable of modulating selected macromolecules of therapeutic importance. Then, such designer peptides are routinely and inexpensively synthesized. The utilization of unusual amino acids is prioritized in the presented approach, to improve the pharmacological properties of the designed peptides. In the proposed study, the design of compounds disrupting the function of selected viral envelope proteins will be attempted. The broader/commercial impacts of this research result from its low costs. De novo design of heavily modified peptides offers a promise of an attractive, affordable drug discovery platform, especially suitable to targeting biomedical problems that are currently neglected, due to the high cost of the competing, currently predominant high throughput screening (HTS) approach to discovering small molecule drugs. Examples include medical conditions characteristic to poorer regions of the world, or rare conditions, which may nevertheless prove important in the context of biodefense. These two areas often overlap. Such medical conditions usually offer a too low financial incentive to justify HTS-based research, yet the effort can be made profitable (in addition to social benefits) if it is based on a changed, less costly discovery paradigm.

这个小企业创新研究（SBIR）第一阶段项目涉及一个新药发现平台的测试和验证。一个原始的算法是用来设计以前未知的肽，能够调制选定的大分子的治疗重要性。然后，这样的设计师肽被常规且廉价地合成。在所提出的方法中，优先考虑利用不寻常的氨基酸，以改善所设计的肽的药理学性质。在拟议的研究中，将尝试设计破坏所选病毒包膜蛋白功能的化合物。这项研究的广泛/商业影响是由于其成本低。从头设计的高度修饰的肽提供了一个有吸引力的，负担得起的药物发现平台的承诺，特别适合于目前被忽视的生物医学问题，由于高成本的竞争，目前占主导地位的高通量筛选（HTS）的方法来发现小分子药物。例子包括世界上较贫穷地区特有的医疗条件，或罕见的条件，但在生物防御方面可能证明是重要的。这两个领域经常重叠。这种医疗条件通常提供太低的经济激励，以证明基于HTS的研究是合理的，但如果它是基于一个改变的，成本较低的发现范式，那么这项工作可以盈利（除了社会效益）。