Sequence-Specific β-Peptide Synthesis by a Rotaxane-Based Molecular Machine

Bo, Guillaume De; Gall, Malcolm A. Y.; Kitching, Matthew O.; Kuschel, Sonja; Leigh, David A.; Tetlow, Daniel J.; Ward, John W.

doi:10.1021/jacs.7b05850

Cited by 63 publications

(25 citation statements)

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“…We targeted a monomer ratio of 11:1, representing an average distance of ~22 Å (unperturbed dimension) 20 between adjacent ester groups. This spacing is similar to the distance (~20 Å) between the building blocks in other rotaxane peptidesynthesizing molecular machines, [8][9][10] which proved to be a good balance between the inter-barrier distance and the overall track length. ATRP polymerization of monomers 5 (220 eq.)…”

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confidence: 60%

“…To broaden the scope and potential utility of ribosome-inspired rotaxane synthesizing machines [8][9][10]16,17 we decided to investigate translating length information from a parent polymer to a molecular-machinesynthesized product, with the aim of making a functional molecular object (Figure 1). Rotaxane-based machines that connect different building blocks in a particular order for sequence-specific synthesis require tracks built through multi-step synthesis.…”

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confidence: 99%

“…Rotaxane-based machines that connect different building blocks in a particular order for sequence-specific synthesis require tracks built through multi-step synthesis. [8][9][10] This is unnecessary for translating length information from a parent track to a new homo-polymer and so for this application we chose for the thread polystyrene bearing leucine ester groups with a narrow molecular weight distribution achieved through atom transfer radical polymerization (ATRP) of styrene with p-leucyloxystyrene. 12 A polystyrene-based track should be inert under the molecular machine operation conditions and is relatively rigid compared to other common polyolefins.…”

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confidence: 99%

“…Machine-track conjugate 1 was deprotected under acidic conditions to reveal the amines and thiol necessary for reaction. The active machine 8 was operated at 65 ˚C in DMF-d 7 for 4 days in the presence of triethylamine and triphenylphosphine (to minimise disulfide formation [8][9][10] ) affording oligoleucine 9 ( Figure 3a). Following a NCL mechanism, the thiolate reacts with the first leucine phenolic ester that blocks the macrocycle's path on the track to form a thioester.…”

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An artificial molecular machine that builds an asymmetric catalyst

et al. 2018

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Biomolecular machines perform types of complex molecular-level tasks that artificial molecular machines can aspire to. The ribosome, for example, translates information from the polymer track it traverses (messenger RNA) to the new polymer it constructs (a polypeptide) . The sequence and number of codons read determines the sequence and number of building blocks incorporated into the biomachine-synthesized polymer. However, neither control of sequence nor the transfer of length information from one polymer to another (which to date has only been accomplished in man-made systems through template synthesis) is easily achieved in the synthesis of artificial macromolecules. Rotaxane-based molecular machines have been developed that successively add amino acids (including β-amino acids ) to a growing peptide chain by the action of a macrocycle moving along a mono-dispersed oligomeric track derivatized with amino-acid phenol esters. The threaded macrocycle picks up groups that block its path and links them through successive native chemical ligation reactions to form a peptide sequence corresponding to the order of the building blocks on the track. Here, we show that as an alternative to translating sequence information, a rotaxane molecular machine can transfer the narrow polydispersity of a leucine-ester-derivatized polystyrene chain synthesized by atom transfer radical polymerization to a molecular-machine-made homo-leucine oligomer. The resulting narrow-molecular-weight oligomer folds to an α-helical secondary structure that acts as an asymmetric catalyst for the Juliá-Colonna epoxidation of chalcones.

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“…To date, the fabrication of AMMs with high complexity and controllable regulation has reached maturity . Beyond fundamental research, chemists have constructed various smart molecular systems with practical functions, either by mimicking biological systems or by collecting synchronous motions in time and space . Herein, we focus on the recent development of intelligent AMMs and summarize the contributions of converting these smart systems into practical functions.…”

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Driving Smart Molecular Systems by Artificial Molecular Machines

Shi

Zhang

Tian

et al. 2020

Advanced Intelligent Systems

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Biomolecular machines are widely present in nature, especially in complex living organisms, and are involved in important biological processes. Inspired by nature and increasingly mature synthetic technologies, a series of artificial molecular machines (AMMs) that exhibit similar processes and functions as biomolecular counterparts have been developed, and to date, some dramatic achievements have been obtained. Herein, the use of AMMs in smart systems and materials with controllable regulations and interesting functions are summarized, presenting the specific micro‐ to macroscale applications in solid surface modification, transmembrane transport, smart catalysts, liquid crystals, artificial molecular muscles, and stimuli‐responsive polymers. The challenges of developing novel complex AMMs with intelligent functions are discussed, and some potential solutions are proposed.

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Amide‐Forming Ligation Reactions

2019

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One of the long‐standing pursuits of synthetic organic chemists is the development of chemical methods for the synthesis of peptides and proteins as tools for understanding biological processes and providing therapeutic solutions to human diseases. The advent of chemoselective ligation reactions for the chemical synthesis of peptides and proteins has enabled synthetic chemists to realize this long‐held dream. In an amide‐forming ligation reaction, two uniquely placed functional groups within the peptide allow peptide or protein segments to be joined in a chemoselective manner with an amide bond. In this chapter, some of the early methods based on principles of the capture/rearrangement strategy for ligation of peptides are catalogued, followed by some of the most versatile and well‐established contemporary methods for the preparation of linear/cyclic peptides and proteins such as the native chemical ligation (NCL) and the α‐ketoacid–hydroxylamine (KAHA) ligation. The chapter concludes with some of the most promising new generation ligation methods such as the potassium acyltrifluoroborate–hydroxylamine (KAT) ligation. The tremendous progress in the past two decades in the development of several ligation methods that rely on a pair of unique functional groups is set to expand the horizons of fully functional proteins and multi‐protein assemblies that are purely synthetically prepared. Although contemporary ligation reactions do not match the speed and efficiency at which proteins are assembled in biological systems, the repertoire of chemoselective amide‐forming ligation methods has already enabled synthetic protein chemistry to surpass biology in terms of chemical and structural diversity.

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Sequence-Specific β-Peptide Synthesis by a Rotaxane-Based Molecular Machine

Cited by 63 publications

References 94 publications

An artificial molecular machine that builds an asymmetric catalyst

An artificial molecular machine that builds an asymmetric catalyst

Driving Smart Molecular Systems by Artificial Molecular Machines

Amide‐Forming Ligation Reactions

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