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

这个小型企业创新研究(SBIR)第一阶段项目涉及一个新药发现平台的测试和验证。一种原始的算法被用来设计以前未知的能够调节选定的具有治疗重要性的大分子的多肽。然后，这样的设计肽被常规地、廉价地合成。在所提出的方法中，优先利用不寻常的氨基酸，以改善所设计的多肽的药理性质。在这项拟议的研究中，将尝试设计破坏选定病毒包膜蛋白功能的化合物。这项研究的更广泛/商业影响源于其低成本。重修饰多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的前景，特别适合于针对目前被忽视的生物医学问题，因为竞争的、目前占主导地位的高通量筛选(HTS)方法用于发现小分子药物的成本很高。例子包括世界上较贫穷地区特有的医疗条件，或罕见的情况，但在生物防御的背景下可能被证明是重要的。这两个领域经常重叠。这样的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，但如果基于一种改变的、成本更低的发现范式，这项努力可以盈利(除了社会效益)。

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.