Jones Douglas S, Silverman Adam P, Cochran Jennifer R
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Trends Biotechnol. 2008 Sep;26(9):498-505. doi: 10.1016/j.tibtech.2008.05.009. Epub 2008 Jul 31.
Ligand-receptor interactions govern myriad cell signaling pathways that regulate homeostasis and ensure that cells respond properly to stimuli. Growth factors, cytokines and other regulatory elements use these interactions to mediate cell responses, including proliferation, migration, angiogenesis, immune responses and cell death. Proteins that inhibit these processes have potential as therapeutics for cancer and autoimmune disorders, whereas proteins that stimulate these processes offer promise in regenerative medicine. Although much of the focus in this area over the past decade has been on monoclonal antibodies, recently there has been increased interest in the use of non-antibody proteins as therapeutic agents. Here, we review recent advances and accomplishments in the use of rational and combinatorial protein engineering approaches to developing ligands and receptors as agonists and antagonists against clinically important targets.
配体-受体相互作用控制着无数调节体内平衡并确保细胞对刺激做出正确反应的细胞信号通路。生长因子、细胞因子和其他调节元件利用这些相互作用来介导细胞反应，包括增殖、迁移、血管生成、免疫反应和细胞死亡。抑制这些过程的蛋白质具有作为癌症和自身免疫性疾病治疗药物的潜力，而刺激这些过程的蛋白质在再生医学中具有前景。尽管在过去十年中该领域的大部分重点都放在单克隆抗体上，但最近人们对使用非抗体蛋白质作为治疗剂的兴趣有所增加。在这里，我们综述了利用合理和组合蛋白质工程方法开发作为针对临床重要靶点的激动剂和拮抗剂的配体和受体方面的最新进展和成果。
