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Issue 5, 2010
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Cooperative DNA binding and assembly by a bZip peptide-amphiphile

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Abstract

The bipartite basic zipper (bZip) GCN4 peptide, containing a leucine zipper and a basic binding region, is a well-studied transcription factor that can be rationally adapted to control dimerization or assembly. We have covalently appended alkyl tails to the C-terminus (leucine zipper terminus) of a bZip sequence, yielding mono- and dialkyl bZip peptide-amphiphiles that allowed us to investigate how molecular design can control the formation of secondary structure and self-assembled structure. We demonstrate that these peptide-amphiphiles exhibit four qualities that are representative of their modular construction. First, circular dichroism confirms that self-assembly of peptide-amphiphiles above the critical micelle concentration (CMC) results in an enhanced α-helical secondary structure as peptide head groups are confined to the assembled interface with high local concentrations. Second, the binding of the peptide-amphiphiles to DNA yields a further increase in secondary structure, where the helicity of the basic binding region is stabilized by forming native-like contacts, an “induced fit mechanism”. Third, competitive fluorescence binding assays show peptide-amphiphiles bind cooperatively to DNA well below the CMC, where DNA templates monomeric binding and hydrophobic forces promote cooperativity, but the ability of the peptide to recognize a specific DNA sequence is not retained. And fourth, SANS results demonstrate the assembly of large lamellar aggregates as peptide-amphiphiles complex with DNA, supporting a structural hypothesis in which peptide-amphiphiles bind to the DNA in a native-like ‘standing’ orientation. These designed synthetic molecular architectures are capable of hierarchical assembly making them useful as functional building blocks that may be applied to a variety of systems, including gene delivery and artificial transcription factors.

Graphical abstract: Cooperative DNA binding and assembly by a bZip peptide-amphiphile

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Publication details

The article was received on 27 Oct 2009, accepted on 22 Dec 2009 and first published on 11 Jan 2010


Article type: Paper
DOI: 10.1039/B922295B
Citation: Soft Matter, 2010,6, 1035-1044
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    Cooperative DNA binding and assembly by a bZip peptide-amphiphile

    R. S. Tu, R. Marullo, R. Pynn, R. Bitton, H. Bianco-Peled and M. V. Tirrell, Soft Matter, 2010, 6, 1035
    DOI: 10.1039/B922295B

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