The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA +1 713 792 3872 ; +1 713 745 0201 ;
Expert Opin Drug Discov. 2009 Jan;4(1):51-9. doi: 10.1517/17460440802628152.
Generation of targeted therapy remains a major challenge in medicine. The development of drugs that can discriminate between tumor cells and non-malignant cells would improve efficacy and reduce general side effects. Phage display allows identification of specific supramolecular complexes that can target therapeutic compounds or imaging agents, both in vitro and in vivo. The use of phage display to identify molecules expressed on the surface of human cancer cells without bias, as well as to provide initial steps toward identification of a ligand/receptor-based map of the human microvasculature, has broad implications for drug discovery in general, especially for cancer therapy.
OBJECTIVE/METHOD: In this review, we discuss the use of phage display technology as a ligand-directed targeting strategy and its applications to drug discovery.
Compared to other existing drug discovery platforms, phage display technology has the advantage to provide valuable clues pointing to target proteins in an unbiased biological context. The result from various display library screenings indicates that in many cases the selected peptide motifs mimic biological ligands. Analysis of peptide motifs targeting a receptor provides a basis for rational drug design of targeted peptidomimetics.
靶向治疗的产生仍然是医学上的一个主要挑战。开发能够区分肿瘤细胞和非恶性细胞的药物将提高疗效并减少一般副作用。噬菌体展示允许鉴定能够靶向治疗化合物或成像剂的特定超分子复合物，无论是在体外还是体内。噬菌体展示用于识别人癌细胞表面表达的分子而没有偏见，并为鉴定基于配体/受体的人类微血管图谱提供了初步步骤，这对一般药物发现具有广泛的意义，特别是对癌症治疗。
目的/方法：在这篇综述中，我们讨论了噬菌体展示技术作为配体定向靶向策略的应用及其在药物发现中的应用。
与其他现有的药物发现平台相比，噬菌体展示技术具有提供有价值线索的优势，这些线索指向无偏生物背景中的靶蛋白。来自各种展示文库筛选的结果表明，在许多情况下，所选肽基序模拟生物配体。针对受体的肽基序分析为靶向肽模拟物的合理药物设计提供了基础。
