Analysis of selected and designed chimeric D- and L-α-helix assemblies.
Biomacromolecules
; 15(9): 3296-305, 2014 Sep 08.
Article
in En
| MEDLINE
| ID: mdl-25072521
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Library
/
Mutation, Missense
/
Multiprotein Complexes
Language:
En
Journal:
Biomacromolecules
Journal subject:
BIOLOGIA MOLECULAR
Year:
2014
Type:
Article
Affiliation country:
Germany