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Editorial Board Chairs: Antonello Mai, Rainer Metternich. Assoc. Editors: David Peralta, Scott Williams (Sr)
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Online ISSN: 1860-7187
January 24, 2012
VIP: Engineering and Functionalization of the Disulfide-Constrained Miniprotein Min-23 as a Scaffold for Diagnostic Applications
Frederic Zoller, Thimon Schwaebel, Annette Markert, Uwe Haberkorn, Walter Mier*
Miniprotein scaffolds gathering interest as antibody mimetics in biomedical research for the development of novel targeting agents for therapy and particularly for diagnostic imaging. These structural templates have been isolated from a wide range of natural sources including plants, animals, and bacteria, and have been investigated as potential lead structures in drug design.
Disulfide-constrained miniproteins—also known as knottins—are particularly advantageous, as their structural properties impart them with outstanding stability, low immunogenicity, and beneficial pharmacokinetic profiles as diagnostic agents. Moreover, knottins can be used as molecular templates for high-throughput screening techniques such as phage or ribosome display, making them ideal scaffolds for the design of new chemical entities.
Walter Mier and co-workers from the German Cancer Research Center (DKFZ) and the University Hospital Heidelberg have revealed the diagnostic potential of this peptide format. They developed a protein engineering strategy for the scaffold Min-23 and evaluated its prerequisites as a diagnostic imaging agent. The results of their work contribute to further developments of knottin peptides as an important scaffold class with broad application in biomedical research.
Received October 26, 2011; published online December 23, 2011, DOI: 10.1002/cmdc.201100497.