Koivunen E, Arap W, Rajotte D, Lahdenranta J, Pasqualini R
Department of Biosciences, University of Helsinki, Viikinkaari, Finland.
J Nucl Med. 1999 May;40(5):883-8.
With the development and maturation of the technology of displaying peptides on bacteriophage, it has become possible to isolate peptide ligands to various targets. In the phage display strategy, up to 10(9) peptides of different permutations are expressed on the surface of filamentous phage. Thus, peptides capable of binding target molecules in vitro and even target tissues in vivo can be identified. In recent years, a series of libraries that display degenerate peptides of different lengths have been constructed, and specific ligands to cell surface receptors, such as integrins, have been isolated. In the in vivo biopanning, peptides targeting distinct organs or tumors have been rescued after intravenous administration of phage libraries into mice. In one application, the isolated peptide ligands have been used to direct a cytotoxic drug to tumor vasculature in mice. Further applications in radioimaging and radiotherapy are being investigated.
随着噬菌体展示肽技术的发展与成熟，分离针对各种靶标的肽配体已成为可能。在噬菌体展示策略中，丝状噬菌体表面可表达多达10⁹种不同排列的肽。因此，能够在体外结合靶分子甚至在体内结合靶组织的肽得以被识别。近年来，已构建了一系列展示不同长度简并肽的文库，并分离出了针对细胞表面受体（如整合素）的特异性配体。在体内淘选过程中，将噬菌体文库静脉注射到小鼠体内后，已筛选出靶向不同器官或肿瘤的肽。在一项应用中，分离出的肽配体已被用于将细胞毒性药物导向小鼠的肿瘤血管。目前正在研究其在放射性成像和放射治疗方面的进一步应用。
