STTR Phase I: Selection of Unnatural Cyclic Peptide Libraries by Messenger Ribonucleic Acid (mRNA) Display

这个小型企业技术转移(STTR)第一阶段项目将探索使用mRNA显示器分离与抗癌靶标血管内皮生长因子(VEGF)相互作用的非核糖体多肽(NRPS)样多肽的可行性。这些多肽是重要的药物治疗药物，具有抗生素和免疫抑制活性。这项STTR研究将开发利用基因技术在体外可选择的多肽鉴定方法。这些多肽表现出非常高的亲和力，显示出高度的结合特异性，但具有类似药物的性质，如蛋白酶抗性和较长的血清半衰期。该项目将验证和优化创造NRPS样多肽的技术，并将产生一种抑制血管内皮生长因子的先导化合物。在商业上，该项目将产生抑制VEGF的NRPS样多肽。这些方法将提供比目前的抗血管内皮生长因子疗法更便宜和更容易的潜在先导化合物。此外，STTR研究验证了合成类似NRPS样肽的环状、非自然多肽库的新技术。这项技术将作为分离其他疗法的药物发现平台。

This Small Business Technology Transfer (STTR) Phase I project will explore the feasibility of using mRNA display to isolate non-ribosomal peptide synthetase (NRPS)-like peptides that interact with the anti-cancer target, vascular endothelial growth factor (VEGF). These peptides are important pharmaceutical therapeutics that exhibit antibiotic and immunosuppressive activities. This STTR research will develop methods for peptide identification that are selectable in vitro using genetic techniques. These peptides exhibit very high affinities, show high specificities of binding, but have drug-like properties such as protease resistance and long serum half-lives. This project will validate and optimize the technology to create NRPS-like peptides and will result in a lead compound for VEGF inhibition.Commercially, this project will result in NRPS-like peptides that inhibit VEGF. These methods will provide potential lead compounds more cheaply and easily than current anti-VEGF therapeutics. Additionally, the STTR research validates new technology to synthesize cyclic, unnatural peptide libraries that resemble NRPS-like peptides. This technology will serve as a drug discover platform for the isolation of other therapeutics.