The Influence of Secondary Structure on Electron Transfer in Peptides

Yu, Jingxian; Horsley, John R.

doi:10.1071/ch13276

Cited by 16 publications

(13 citation statements)

References 22 publications

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“…Circular dichroism and NMR analysis reveals that the backbone of folds into a 3 14 -helical structure, which is consistent with geometry optimization 21,24 using the density functional theory (DFT) method. Calculations for 1 suggest that it adopts an ill-defined conformation.…”

Section: Electron Transfer Dynamics: Superexchange Vs Hoppingsupporting

confidence: 72%

Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective

Horsley

2018

Acc. Chem. Res.

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Molecular electronics is at the forefront of interdisciplinary research, offering a significant extension of the capabilities of conventional silicon-based technology as well as providing a possible stand-alone alternative. Bio-inspired molecular electronics is a particularly intriguing paradigm, as charge transfer in proteins/peptides, for example, plays a critical role in the energy storage and conversion processes for all living organisms. However, the structure and conformation of even the simplest protein is extremely complex, and therefore, synthetic model peptides comprising well-defined geometry and predetermined functionality are ideal platforms to mimic nature for the elucidation of fundamental biological processes while also enhancing the design and development of single-peptide electronic components. In this Account, we first present intramolecular electron transfer within two synthetic peptides, one with a well-defined helical conformation and the other with a random geometry, using electrochemical techniques and computational simulations. This study reveals two definitive electron transfer pathways (mechanisms), the natures of which are dependent on secondary structure. Following on from this, electron transfer within a series of well-defined helical peptides, constrained by either Huisgen cycloaddition, ring-closing metathesis, or a lactam bridge, was determined. The electrochemical results indicate that each constrained peptide, in contrast to a linear counterpart, exhibits a remarkable shift of the formal potential to the positive (>460 mV) and a significant reduction of the electron transfer rate constant (up to 15-fold), which represent two distinct electronic "on/off" states. High-level calculations demonstrate that the additional backbone rigidity provided by the side-bridge constraints leads to an increased reorganization energy barrier, which impedes the vibrational fluctuations necessary for efficient intramolecular electron transfer through the peptide backbone. Further calculations reveal a clear mechanistic transition from hopping to superexchange (tunneling) stemming from side-bridge gating. We then extended our research to fine-tuning of the electronic properties of peptides through both structural and chemical manipulation, to reveal an interplay between electron-rich side chains and backbone rigidity on electron transfer. Further to this, we explored the possibility that the side-bridge constraints present in our synthetic peptides provide an additional electronic transport pathway, which led to the discovery of two distinct forms of quantum interferometer. The effects of destructive quantum interference appear essentially through both the backbone and an alternative tunneling pathway provided by the side bridge in the constrained β-strand peptide, as evidenced by a correlation between electrochemical measurements and conductance simulations for both linear and constrained β-strand peptides. In contrast, an interplay between quantum interference effects and vibrational fluctuations ...

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Section: Electron Transfer Dynamics: Superexchange Vs Hoppingsupporting

confidence: 72%

Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective

Horsley

2018

Acc. Chem. Res.

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“…Electron transfer in proteins plays an important role in a wide range of metabolic processes at the cellular level. 1 , 2 Many factors have been shown to influence this electron transfer, including the distance separating the electron donor and acceptor, 3 − 5 the extent of secondary structure, 6 , 7 dipole moment, 8 − 10 and the nature of the constituent amino acid side chains. 11 − 14 Of particular significance is the suggestion that peptides can undergo electron transfer via either a bridge-assisted superexchange or an electron hopping mechanism.…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Interplay of Backbone Rigidity and Electron Rich Side-Chains on Electron Transfer in Peptides: The Realization of Tunable Molecular Wires

Horsley

Moore

et al. 2014

J. Am. Chem. Soc.

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Electrochemical studies are reported on a series of peptides constrained into either a 310-helix (1–6) or β-strand (7–9) conformation, with variable numbers of electron rich alkene containing side chains. Peptides (1 and 2) and (7 and 8) are further constrained into these geometries with a suitable side chain tether introduced by ring closing metathesis (RCM). Peptides 1, 4 and 5, each containing a single alkene side chain reveal a direct link between backbone rigidity and electron transfer, in isolation from any effects due to the electronic properties of the electron rich side-chains. Further studies on the linear peptides 3–6 confirm the ability of the alkene to facilitate electron transfer through the peptide. A comparison of the electrochemical data for the unsaturated tethered peptides (1 and 7) and saturated tethered peptides (2 and 8) reveals an interplay between backbone rigidity and effects arising from the electron rich alkene side-chains on electron transfer. Theoretical calculations on β-strand models analogous to 7, 8 and 9 provide further insights into the relative roles of backbone rigidity and electron rich side-chains on intramolecular electron transfer. Furthermore, electron population analysis confirms the role of the alkene as a “stepping stone” for electron transfer. These findings provide a new approach for fine-tuning the electronic properties of peptides by controlling backbone rigidity, and through the inclusion of electron rich side-chains. This allows for manipulation of energy barriers and hence conductance in peptides, a crucial step in the design and fabrication of molecular-based electronic devices.

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“…As seen in Figure 4 a, the dependence is not linear; this was explained by the authors as observing the hopping mechanism (existing theoretical models for ET are discussed in Section 5). Evidence for the importance of the secondary structure, and subsequently, the amount of hydrogen bonds, for efficient ET across the α helix was reported by Abell and co‐workers,62 who followed electrochemical ET across a poly‐Aib peptide. They observed that the dependence of the ET rate on the distance between Fc and the electrode became very shallow, only after the formation of the helical structure, whereas in very short peptides, in which the helical structure cannot be formed, this dependence is very steep (Figure 4 b).…”

Section: Electrochemically Induced Etmentioning

confidence: 92%

Electron Transfer across Helical Peptides

Amdursky

2015

ChemPlusChem

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Electron transfer (ET) across proteins is one of the fundamental processes in nature. While trying to decipher and understand natural ET, much scientific effort has been employed in scaling down the process to the role of the elementary secondary‐structure units of proteins, that is, β sheets and α helices. Among these two motifs, the vast majority of studies have focused on α‐helical peptides because they require fewer amino acids for formation, they can be easily assembled on surfaces, and they can be easily functionalized. Herein, the focus is only on ET across α‐helical peptides, not only because of the reasons discussed, but also because they are one of the most promising biological molecules for integration into ET‐based bioelectronic devices. The different methodologies used to follow ET across the peptides, namely, photoinduced ET, electrochemistry, and solid‐state conductivity measurements (referred to as electron transport, ETp), are reviewed and discussed. In this context, the fundamental differences between the different methodologies, the appropriate interpretation of the results, and possible mechanisms to describe the ET(p) process in each methodology are discussed. Furthermore, possible functionalization of the helical peptides to modify and control their (opto‐)electronic properties is reviewed.

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The Influence of Secondary Structure on Electron Transfer in Peptides

Cited by 16 publications

References 22 publications

Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective

Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective

Unraveling the Interplay of Backbone Rigidity and Electron Rich Side-Chains on Electron Transfer in Peptides: The Realization of Tunable Molecular Wires

Electron Transfer across Helical Peptides

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