Combination of Phage Display and Molecular Grafting Generates Highly Specific Tumor-Targeting Miniproteins

• Published in: Angewandte Chemie International Edition Vol. 51; no. 52; pp. 13136 - 13139
• Main Authors: Zoller, Frederic, Markert, Annette, Barthe, Philippe, Zhao, Wenye, Weichert, Wilko, Askoxylakis, Vasileios, Altmann, Annette, Mier, Walter, Haberkorn, Uwe
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 21-12-2012; WILEY‐VCH Verlag; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Edition: International ed. in English
• Subjects: Affinity; Amino Acid Sequence; Binding; Cell Line, Tumor; diagnostic agents; drug discovery; Fluorescent Dyes - chemistry; Grafting; Human Umbilical Vein Endothelial Cells; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins - chemistry; Intracellular Signaling Peptides and Proteins - metabolism; Life Sciences; Ligands; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Microscopy, Confocal; Molecular Sequence Data; Neoplasms - pathology; Peptide Library; Peptides; Peptides - chemistry; Peptides - metabolism; Protein Binding; protein structure; radiochemical analysis; Scaffolds; Stability; Surface Plasmon Resonance; Trypsin inhibitors; Trypsin Inhibitors - chemistry; Trypsin Inhibitors - metabolism
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201203857

Frankenstein′s peptide: The grafting of the binding domain from miniprotein Min‐23 into the sunflower trypsin inhibitor (SFTI‐I) peptide scaffold (see scheme) preserved its in vitro and in vivo binding specificity and proteolytic stability. The combination of these peptides was shown to be tumor‐specific with a good binding affinity for delta‐like ligand 4 (Dll4) protein. The use of SFTI‐I as a peptide scaffold is ideal for hit‐to‐lead development.