TY  - JOUR
A1  - Bartoloni, Marco
A1  - Jin, Xian
A1  - Marcaida, Maria José
A1  - Banha, Joao
A1  - Dibonaventura, Ivan
A1  - Bongoni, Swathi
A1  - Bartho, Kathrin
A1  - Gräbner, Olivia
A1  - Sefkow, Michael
A1  - Darbre, Tamis
A1  - Reymond, Jean-Louis
T1  - Bridged bicyclic peptides as potential drug scaffolds
BT  - synthesis, structure, protein binding and stability
JF  - Chemical Science
N2  - 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.
Y1  - 2015
U6  - https://doi.org/10.1039/C5SC01699A
SN  - 2041-6520
SN  - 2041-6539
VL  - 10
IS  - 6
SP  - 5473
EP  - 5490
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  -