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

这个小企业创新研究（SBIR）的第一阶段项目包括测试和验证一个新的药物发现平台。一个原始的算法是用来设计以前未知的肽，能够调节选定的大分子治疗的重要性。然后，这样的设计肽是常规和廉价的合成。在提出的方法中，利用不寻常的氨基酸是优先考虑的，以改善所设计肽的药理学性质。在拟议的研究中，将尝试设计破坏选定病毒包膜蛋白功能的化合物。这项研究的广泛/商业影响源于其低成本。重修饰肽的从头设计提供了一个有吸引力的、负担得起的药物发现平台，特别适合针对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）方法来发现小分子药物。例子包括世界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的经济激励太低，不足以证明基于hts的研究是合理的，然而，如果基于一种改变的、成本更低的发现范式，这种努力是可以盈利的（除了社会效益之外）。

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.