TY  - JOUR
A1  - Kuekenshoener, Tim
A1  - Hagemann, Urs B.
A1  - Wohlwend, Daniel
A1  - Raeuber, Christina
A1  - Baumann, Tobias
A1  - Keller, Sandro
A1  - Einsle, Oliver
A1  - Mueller, Kristian M.
A1  - Arndt, Katja Maren
T1  - Analysis of Selected and Designed Chimeric D- and L-alpha-Helix Assemblies
JF  - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences
N2  - D-Peptides have been attributed pharmacological advantages over regular L-peptides, yet design rules are largely unknown. Based on a designed coiled coil-like D/L heterotetramer, named L-Base/D-Acid, we generated a library offering alternative residues for interaction with the D-peptide. Phage display selection yielded one predominant peptide, named HelixA, that differed at 13 positions from the scaffold helix. In addition to the observed D-/L-heterotetramers, ratio-dependent intermediate states were detected by isothermal titration calorimetry. Importantly, the formation of the selected HelixA/D-Acid bundle passes through fewer intermediate states than L-Base/D-Acid. Back mutation of HelixA core residues to L-Base (HelixLL) revealed that the residues at e/g-positions are responsible for the different intermediates. Furthermore, a Val-core variant (PeptideVV) was completely devoid of binding D-Acid, whereas an Ile-core helix (HelixII) interacted with D-Acid in a significantly more specific complex than L-Base.
Y1  - 2014
U6  - https://doi.org/10.1021/bm5006883
SN  - 1525-7797
SN  - 1526-4602
VL  - 15
IS  - 9
SP  - 3296
EP  - 3305
PB  - American Chemical Society
CY  - Washington
ER  -