Analysis of Selected and Designed Chimeric D- and L-alpha-Helix Assemblies
- 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.
Author details: | Tim Kuekenshoener, Urs B. Hagemann, Daniel Wohlwend, Christina Raeuber, Tobias BaumannORCiD, Sandro Keller, Oliver Einsle, Kristian M. Mueller, Katja Maren ArndtORCiDGND |
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DOI: | https://doi.org/10.1021/bm5006883 |
ISSN: | 1525-7797 |
ISSN: | 1526-4602 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/25072521 |
Title of parent work (English): | Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences |
Publisher: | American Chemical Society |
Place of publishing: | Washington |
Publication type: | Article |
Language: | English |
Year of first publication: | 2014 |
Publication year: | 2014 |
Release date: | 2017/03/27 |
Volume: | 15 |
Issue: | 9 |
Number of pages: | 10 |
First page: | 3296 |
Last Page: | 3305 |
Funding institution: | Collaborative Research Centre, in the Emmy-Noether Program of the German Research Foundation (DFG) [(SFB) 850, Ar 373]; European Research Council |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
Peer review: | Referiert |