High-Resolution Structure of a β-Peptide Bundle

Daniels, Douglas S.; Petersson, E. James; Qiu, Jade X.; Schepartz, Alanna

doi:10.1021/ja068678n

Cited by 199 publications

(180 citation statements)

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“…[13] b-Peptides were used in this study as they are known to adopt helical secondary structures with high predictability, structural diversity, and stability. [14][15][16][17][18] These structures are ideal for studying the fundamental mechanisms of electron transport, but they have as yet received scant attention. In this case, an N-terminal tert-butyl hydroperoxide was used as the electron acceptor and a C-terminal p-cyanobenzamide as the donor.…”

Section: Electron Transfer Dynamicsmentioning

confidence: 99%

The Influence of Secondary Structure on Electron Transfer in Peptides

Horsley

2013

Aust. J. Chem.

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A series of synthetic peptides containing 0-5 a-aminoisobutyric acid (Aib) residues and a C-terminal redox-active ferrocene was synthesised and their conformations defined by NMR and circular dichroism. Each peptide was separately attached to an electrode for subsequent electrochemical analysis in order to investigate the effect of peptide chain length (distance dependence) and secondary structure on the mechanism of intramolecular electron transfer. While the shorter peptides (0-2 residues) do not adopt a well defined secondary structure, the longer peptides (3-5 residues) adopt a helical conformation, with associated intramolecular hydrogen bonding. The electrochemical results on these peptides clearly revealed a transition in the mechanism of intramolecular electron transfer on transitioning from the ill-defined shorter peptides to the longer helical peptides. The helical structures undergo electron transfer via a hopping mechanism, while the shorter ill-defined structures proceeded via an electron superexchange mechanism. Computational studies on two b-peptides PCB-(b 3 Val-b 3 Ala-b 3 Leu) n -NHC(CH 3 ) 2 OOtBu (n ¼ 1 and 2; PCB ¼ p-cyanobenzamide) were consistent with these observations, where the n ¼ 2 peptide adopts a helical conformation and the n ¼ 1 peptide an ill-defined structure. These combined studies suggest that the mechanism of electron transfer is defined by the extent of secondary structure, rather than merely chain length as is commonly accepted.

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Section: Electron Transfer Dynamicsmentioning

confidence: 99%

The Influence of Secondary Structure on Electron Transfer in Peptides

Horsley

2013

Aust. J. Chem.

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“…The refined model is octameric and remarkably similar to the octameric Zwit-1F and Zwit-1F* structures ( Figure 6). 32 The Acid-1Y* model consists of eight 3 14 -helices organized into two tetramers related by a two-fold rotation axis ( Figure 6A). The design for the β-peptide quaternary structure was based on the packing of leucine residues in coiled coils, a motif that promotes oligomerization of natural proteins.…”

Section: Side Chain Packing Drives Octamer Formationmentioning

confidence: 99%

“…[31][32][33] The β-peptide bundles formed from the sequences Zwit-1F, its iodinated analogue Zwit-1F*, and the 1:1 mixture of Acid-1F and Base-1F ( Figure 1) were characterized extensively using biophysicalmethodsandhighresolutionstructuredetermination. [31][32][33][34] Here, we characterize the related homo-oligomers Acid-1Y and its iodinated analogue Acid-1Y* using analytical ultracentrifugation (AU), circular dichroism (CD), differential scanning calorimetry (DSC), 1-anilino-8-naphthalenesulfonate (ANS) binding, NMR spectroscopy, and X-ray crystallography. Acid-1Y and Acid-1Y* assemble into stable, well-folded, octameric bundles whose three-dimensional structures are remarkably similar to those of Zwit-1F 32 and the mixture of Acid-1F and Base-1F (D. Daniels, J. Qiu, and A. Schepartz, manuscript in preparation), indicating the robust nature of the octamer fold.…”

Section: Introductionmentioning

confidence: 99%

Biophysical and Structural Characterization of a Robust Octameric β-Peptide Bundle

et al. 2007

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Proteins composed of α-amino acids are essential components of the machinery required for life. Stanley Miller's renowned electric discharge experiment provided evidence that an environment of methane, ammonia, water, and hydrogen was sufficient to produce α-amino acids. This reaction also generated other potential protein building blocks such as the β-amino acid β-glycine (also known as β-alanine); however, the potential of these species to form complex ordered structures that support functional roles has not been widely investigated. In this report we apply a variety of biophysical techniques, including circular dichroism, differential scanning calorimetry, analytical ultracentrifugation, NMR and X-ray crystallography, to characterize the oligomerization of two 12-mer β 3 -peptides, Acid-1Y and Acid-1Y*. Like the previously reported β 3 -peptide Zwit-1F, Acid-1Y and Acid-1Y* fold spontaneously into discrete, octameric quaternary structures that we refer to as β-peptide bundles. Surprisingly, the Acid-1Y octamer is more stable than the analogous Zwit-1F octamer, in terms of both its thermodynamics and kinetics of unfolding. The structure of Acid-1Y, reported here to 2.3 Å resolution, provides intriguing hypotheses for the increase in stability. To summarize, in this work we provide additional evidence that nonnatural β-peptide oligomers can assemble into cooperatively folded structures with potential application in enzyme design, and as medical tools and nanomaterials. Furthermore, these studies suggest that nature's selection of α-amino acid precursors was not based solely on their ability to assemble into stable oligomeric structures.

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“…Synthetic foldamers have been found to exhibit well-defined conformational ordering (16,35) and recent investigations have produced molecular architectures that emulate protein secondary and tertiary structures (36)(37)(38). Further advancement of foldamers will benefit from design strategies that enable sophisticated functions such as catalysis (39).…”

Section: Resultsmentioning

confidence: 99%

Folded biomimetic oligomers for enantioselective catalysis

Maayan

Ward

Kirshenbaum

2009

Proc. Natl. Acad. Sci. U.S.A.

191

143

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Many naturally occurring biopolymers (i.e., proteins, RNA, DNA) owe their unique properties to their well-defined three-dimensional structures. These attributes have inspired the design and synthesis of folded architectures with functions ranging from molecular recognition to asymmetric catalysis. Among these are synthetic oligomeric peptide (''foldamer'') mimics, which can display conformational ordering at short chain lengths. Foldamers, however, have not been explored as platforms for asymmetric catalysis. This report describes a library of synthetic helical ''peptoid'' oligomers that enable enantioselective transformations at an embedded achiral catalytic center, as illustrated by the oxidative kinetic resolution of 1-phenylethanol. In an investigation aimed at elucidating key structure-function relationships, we have discovered that the enantioselectivity of the catalytic peptoids depends on the handedness of the asymmetric environment derived from the helical scaffold, the position of the catalytic center along the peptoid backbone, and the degree of conformational ordering of the peptoid scaffold. The transfer of chiral information from a folded scaffold can enable the use of a diverse assortment of embedded achiral catalytic centers, promising a generation of synthetic foldamer catalysts for enantioselective transformations that can be performed under a broad range of reaction environments.catalyst ͉ foldamer ͉ oxidative kinetic resolution ͉ peptoid T he unique capabilities of biopolymers, which stem from their well-defined three-dimensional structures, have been a source of inspiration for the design and synthesis of functional chemical systems (1). A variety of strategies have been explored for de novo construction of modular catalysts that enable chemical selectivity, regioselectivity, or enantioselectivity as a consequence of their structural organization. For example, synthetic peptides equipped with catalytic artificial amino acid groups or transition metal sites have been demonstrated to be effective enantioselective catalysts due to the proximity of the catalytic sites to the asymmetric environment created by their backbone (2-4). Similarly, it has been reported that nucleic acids can be used as chiral scaffolds for asymmetric synthesis and catalysis (5, 6). A recent investigation of DNA-based asymmetric catalysis relies on the noncovalent association of an achiral metal catalyst at unspecified sites along a DNA backbone, creating a chiral environment about the catalytic center that results in enantioselective transformations (7,8). Despite these advances, there remains a need for robust systems that permit rational design of versatile sequences and facile synthesis of libraries for high-throughput screening and optimization of catalytic performance.In living systems, biopolymer catalysts have evolved to accelerate specific biologically relevant transformations. In contrast, synthetic catalysts must often be designed for nonbiological transformations to be performed in abiotic solvents, pH regime...

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High-Resolution Structure of a β-Peptide Bundle

Cited by 199 publications

References 22 publications

The Influence of Secondary Structure on Electron Transfer in Peptides

The Influence of Secondary Structure on Electron Transfer in Peptides

Biophysical and Structural Characterization of a Robust Octameric β-Peptide Bundle

Folded biomimetic oligomers for enantioselective catalysis

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