Analysis of Selected and Designed Chimeric D- and L-alpha-Helix Assemblies
| Autor: | Tim Kükenshöner, Kristian M. Müller, Katja M. Arndt, Christina Räuber, Daniel Wohlwend, Oliver Einsle, Urs B. Hagemann, Sandro Keller, Tobias Baumann |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
chemistry.chemical_classification
Mutation Phage display Polymers and Plastics Chemistry Stereochemistry Mutation Missense Bioengineering Isothermal titration calorimetry Peptide medicine.disease_cause Heterotetramer Protein Structure Secondary Biomaterials Protein structure Amino Acid Substitution Peptide Library Multiprotein Complexes Helix Materials Chemistry medicine Peptide library Institut für Biochemie und Biologie |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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