Bridged bicyclic peptides as potential drug scaffolds
- Double cyclization of short linear peptides obtained by solid phase peptide synthesis was used to prepare bridged bicyclic peptides (BBPs) corresponding to the topology of bridged bicyclic alkanes such as norbornane. Diastereomeric norbornapeptides were investigated by 1H-NMR, X-ray crystallography and CD spectroscopy and found to represent rigid globular scaffolds stabilized by intramolecular backbone hydrogen bonds with scaffold geometries determined by the chirality of amino acid residues and sharing structural features of β-turns and α-helices. Proteome profiling by capture compound mass spectrometry (CCMS) led to the discovery of the norbornapeptide 27c binding selectively to calmodulin as an example of a BBP protein binder. This and other BBPs showed high stability towards proteolytic degradation in serum.
Author details: | Marco Bartoloni, Xian Jin, Maria José Marcaida, Joao Banha, Ivan Dibonaventura, Swathi Bongoni, Kathrin Bartho, Olivia Gräbner, Michael Sefkow, Tamis Darbre, Jean-Louis Reymond |
---|---|
DOI: | https://doi.org/10.1039/C5SC01699A |
ISSN: | 2041-6520 |
ISSN: | 2041-6539 |
Title of parent work (English): | Chemical Science |
Subtitle (German): | synthesis, structure, protein binding and stability |
Publisher: | Royal Society of Chemistry |
Place of publishing: | Cambridge |
Publication type: | Article |
Language: | English |
Date of first publication: | 2015/06/13 |
Publication year: | 2015 |
Publishing institution: | Universität Potsdam |
Release date: | 2015/09/25 |
Volume: | 10 |
Issue: | 6 |
First page: | 5473 |
Last Page: | 5490 |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Peer review: | Referiert |
Publishing method: | Open Access |
Grantor: | RSC |
License (English): | Creative Commons - Namensnennung 3.0 Unported |
External remark: | Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 197 |