کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5216542 | 1383267 | 2014 | 7 صفحه PDF | دانلود رایگان |
Aberrant expression of the epidermal growth factor receptor Her2 has been implicated in various malignancies including breast cancer. Monoclonal antibodies and an antibody-drug conjugate targeting Her2 have found wide clinical application. Herein, we aimed at developing Her2-specifc ligands based on peptides that have a 100-fold smaller molecular weight than antibodies. Such peptides could potentially offer advantages in the development of ligand-drug conjugates, such as ease of synthesis and conjugation, higher molecule-per-mass ratios, and better tumor penetration. Panning of large bicyclic peptide phage display libraries against Her2 yielded a range of Her2-specific ligands having different formats and binding motifs. Strong sequence similarities among several of the isolated peptides indicated that they interact with Her2 in a specific manner. The best bicyclic peptide obtained after affinity maturation bound Her2 with a KD of 304Â nM. The diverse peptide ligands may offer valuable starting points for the development of high-affinity Her2 binders with potential application for tumor imaging and therapy.
Journal: Tetrahedron - Volume 70, Issue 42, 21 October 2014, Pages 7733-7739