Editorial overview: Synthetic Biomolecules

Saebi

Poskus

et al. 2020

Science

247

250

Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. Here, we report highly efficient chemistry matched with an automated fast-flow instrument for the direct manufacturing of peptide chains up to 164 amino acids long over 327 consecutive reactions. The machine is rapid: Peptide chain elongation is complete in hours. We demonstrate the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials display biophysical and enzymatic properties comparable to the biologically expressed proteins. High-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome.

Section: Optimized Afps Enables Routine Access To Peptides In the Size Range Of Single Domain Proteins (~130 Aas)mentioning

confidence: 99%

Section: Optimized Afps Enables Routine Access To Single-domain Prote...mentioning

confidence: 99%

Synthesis of proteins by automated flow chemistry

Saebi

Poskus

et al. 2020

Science

247

250

“…For any work in which chemical protein synthesis is a significant focus, best practices for the characterization of synthetic products should be followed. [ 51 ]…”

Section: Recent Advances and Developmentsmentioning

confidence: 99%

Flow‐based SPPS for protein synthesis: A perspective

Gates

2020

Peptide Science

Flow‐based approaches to solid phase peptide synthesis (SPPS) have been pursued since the method's early days, with anticipated gains in speed, reaction monitoring, and ease of automation. Here, we discuss how these advantages are being realized by synthesis at elevated temperature, facilitated by a 'preheat/activation' loop. This important modification both accelerates peptide synthesis—providing a wealth of new data from in‐line monitoring—and in conjunction with an optimized protocol, extends the length of peptides routinely accessible by stepwise synthesis. Streamlined synthesis of longer peptides will address a major challenge in chemical protein synthesis: preparation of peptide segments for use in chemical ligation. The context of recent results in flow‐based SPPS is discussed, highlighting remaining challenges and future opportunities.

Section: Fig 5 Afps Yields Milligram Quantities Of Proteins In Hoursmentioning

confidence: 99%

Synthesis of Proteins by Automated Flow Chemistry

Saebi

Poskus

et al. 2020

Preprint

<p>Ribosomes produce most proteins of living cells in seconds. Here we report highly efficient chemistry matched with an automated fast-flow instrument for the direct manufacturing of peptide chains up to 164 amino acids over 328 consecutive reactions. The machine is rapid - the peptide chain elongation is complete in hours. We demonstrate the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials display biophysical and enzymatic properties comparable to the biologically expressed proteins. High-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome.<i></i></p>