Sequence-Specific Peptide Synthesis by an Artificial Small-Molecule Machine

Lewandowski, Bartosz; Bo, Guillaume De; Ward, John W.; Papmeyer, Marcus; Kuschel, Sonja; Aldegunde, María J.; Gramlich, Philipp M. E.; Heckmann, Dominik; Goldup, Stephen M.; D’Souza, Daniel M.; Fernandes, Antony E.; Leigh, David A.

doi:10.1126/science.1229753

Cited by 666 publications

(464 citation statements)

References 32 publications

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“…73 There are many options for the two communities to consider, including: nano-printing of host-guest arrays for rapid analysis of multiple, related complexation events such as on the surface of a protein, and; probing multistep processes such as those of artificial molecular machines. 74,75 …”

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confidence: 99%

Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry

et al. 2017

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Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry. AbstractOn planet Earth, water is everywhere: the majority of the surface is covered with it; it is a key component of all life; its vapor and droplets fill the lower atmosphere; even rocks contain it and undergo geomorphological changes because of it. A community of physical scientists largely drives studies of the chemistry of water and aqueous solutions, with expertise in biochemistry, spectroscopy, and computer modeling. More recently however, supramolecular chemistry -with its expertise in macrocyclic synthesis and measuring supramolecular interactions -have renewed their interest in water-mediated non-covalent interactions. These two groups offer complementary expertise that, if harnessed, offers to accelerate our understanding of aqueous supramolecular chemistry and water writ large. This review summarizes the state-of-the-art of the two fields, and highlights where there is latent chemical space for collaborative exploration by the two groups. 4Water is ubiquitous and essential to life on planet Earth. A full understanding of aqueous solutions is therefore of significance to a wide range of fields within the atmospheric, environmental, biological and geological sciences. Within the chemical sciences, a deeper appreciation of how non-covalent interactions and chemical transformations are influenced by water would benefit a variety of fields. However, as we highlight here, there are many open questions regarding the chemical and physical properties of aqueous solutions.The aqueous realm is frequently bifurcated into the Hofmeister and hydrophobic effects, phenomena that respectively deal with the properties of solutions of salts and relatively nonpolar molecules. However, it is becoming increasingly evident that these areas do in fact frequently overlap; two prime examples being the accumulation of large polarizable anions at the air-water interface, 1-5 and the favorable interactions of polarizable anions with non-polar surfaces. [6][7][8][9][10][11][12][13][14][15] Thus the hydrophobic and Hofmeister effects are but part of a greater continuum of aqueous supramolecular chemistry, with many important and outstanding questions regarding the influence of the different kinds of non-covalent interactions involved.Studies of water and aqueous solutions have mostly been driven by the physical sciences community, a broad range of scientists whose expertise in spectroscopy, computer modeling, and biochemistry (to name just three areas) has generally not involved macrocycles or host molecules in general. However, for some time now, supramolecular chemists -with their expertise in macrocyclic synthesis and measuring weak non-covalent interactions -have been travelling a parallel course of exploration. This Review, inspired by discussions between sixteen members of each community at a recent workshop, 16 is an attempt to summarize what we know about aqueous solutions, what we do not know about them, and where the two communit...

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confidence: 99%

Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry

et al. 2017

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“…A considerable number of biological and chemical approaches have been developed for preventing or minimizing the formation of error sequences. [28][29][30][31][32][33][34] From the process operation perspective, two key decision variables in MEPS are the reaction extent for each coupling and the extent of removal of amino acid and piperidine before a new coupling. These variables have significant implications for the formation of general error sequences (i.e.…”

Section: P a G Ementioning

confidence: 99%

Implication of Side Reactions in Iterative Biopolymer Synthesis: The Case of Membrane Enhanced Peptide Synthesis

Chen

Sharifzadeh

Shah

et al. 2017

Ind. Eng. Chem. Res.

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Membrane enhanced peptide synthesis (MEPS) improves conventional liquid phase synthesis by purifying intermediate products via filtration. A challenging aspect of MEPS is the propagation of unreacted materials and by-products throughout the iterative synthesis. In this study, we first develop and validate a model of MEPS. The model is then applied to investigate the implications of sidereactions (i.e. formation of error sequences) due to incomplete reaction and insufficient removal of amino acids after coupling. Sensitivity analysis shows that increasing the reaction extent for all couplings from 90% to 100% reduces the yield of truncated sequences from 29% to 0%. The formation of repeating sequences is found to be negligible in all case studies due to the large diavolume of postdeprotection diafiltration. This study provides useful insights into the operation of MEPS with particular emphasis on the control of error sequence formation. These insights are transferable to other sequencecontrolled biopolymer syntheses.

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“…Perhaps the prime example of the nano approach is Leigh's molecular assembly line 18 . Inspired by the ribosome, it is based on a rotaxane system that picks up amino acids from its axle and adds them to a growing peptide chain.…”

Section: Pump It Upmentioning

confidence: 99%

The tiniest Lego: a tale of nanoscale motors, rotors, switches and pumps

Peplow¹

2015

Nature

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Sequence-Specific Peptide Synthesis by an Artificial Small-Molecule Machine

Cited by 666 publications

References 32 publications

Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry

Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry

Implication of Side Reactions in Iterative Biopolymer Synthesis: The Case of Membrane Enhanced Peptide Synthesis

The tiniest Lego: a tale of nanoscale motors, rotors, switches and pumps

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