Abstract
We propose that peptides are highly versatile platforms for the precise design of supramolecular metal architectures, and particularly, for the controlled assembly of helicates. In this context, we show that the bacteriophage T4 Fibritin foldon (T4Ff) can been engineered on its N-terminus with metal-chelating 2,2′-bipyridine units that stereoselectively assemble in the presence of Fe(II) into parallel, three-stranded peptide helicates with preferred helical orientation. Modeling studies support the proposed self-assembly and the stability of the final helicate. Furthermore, we show that these designed mini-metalloproteins selectively recognize three-way DNA junctions over double-stranded DNA.
Highlights
Peptides are excellent supramolecular building blocks that encode precise structural and functional information within their amino acid sequence
As an alternative platform to the ubiquitous leucine zippers, we focused our attention on the C-terminal domain of the bacteriophage T4 Fibritin foldon (T4Ff), a trimeric β-propellerlike structure formed by the self-assembly of a short 27-amino acid peptide (Tao et al, 1997; Papanikolopoulou et al, 2004; Habazettl et al, 2009)
We have previously described an Fmocprotected 2,2′-bipyridine dipeptide derivative that can be readily implemented into standard Fmoc solid-phase peptide synthesis (SPPS) protocols, and have showed that the structure of this chelating unit, in which the 2,2′-bipyridine ligand is integrated in the peptide backbone, effectively couples the conformational preferences of the peptide chain with the geometry of the resulting metal complexes (Rama et al, 2012; Gamba et al, 2013, 2014, 2016; Salvadó et al, 2016)
Summary
Peptides are excellent supramolecular building blocks that encode precise structural and functional information within their amino acid sequence. Helicates are discrete metal complexes in which one or more organic ligands are coiled around—and coordinating—two or more metal ions (Piguet et al, 1997; Albrecht, 2001, 2005) as a result of ligand coiling, helicates are inherently chiral species that can appear as two enantiomers according to the orientation in which the ligands twist around the helical axis defined by the metal centers Besides their intrinsic interest in basic supramolecular chemistry, helicates have shown promising DNA-binding properties that have been associated with antimicrobial and antitumoral effects (Howson et al, 2012; Kaner et al, 2015). Jean-Marie Lehn (Lehn et al, 1987; Ulijn and Smith, 2008), helicates are still not viable alternatives to traditional
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