Synthesis of proteins by automated flow chemistry

• DOI: 10.1126/science.abb2491
• Publication Date: 2020-05-28T23:05:29Z
• Authors: N. Hartrampf; A. Saebi; M. Poskus; Z. P. Gates; A. J. Callahan; A. E. Cowfer; S. Hanna; S. Antilla; C. K. Schissel; A. J. Quartararo; X. Ye; A. J. Mijalis; M. D. Simon; A. Loas; S. Liu; C. Jessen; T. E. Nielsen; B. L. Pentelute
• Keywords: 0301 basic medicine; Protein Folding; 0303 health sciences; 03 medical and health sciences; Protein Domains; Proteins; Peptides; Solid-Phase Synthesis Techniques

Fully synthetic whole proteins in reach

Solid-phase peptide synthesis of homogeneous peptides longer than about 50 amino acids has been a long-standing challenge because of inefficient coupling and side reactions. Hartrampf et al. used an automated chemistry platform to optimize fast-flow peptide synthesis and were able to produce fully synthetic single-domain proteins (see the Perspective by Proulx). The targets included proinsulin and enzymes such as barnase and a version of HIV-1 protease containing multiple noncanonical amino acids. Refolded peptides were nearly indistinguishable from recombinant proteins, and the synthesized enzymes had activity close to that of their ribosomally synthesized counterparts. This method will enable fast, on-demand synthesis of small proteins with a vastly expanded pool of precursor amino acids.

Science , this issue p. 980 ; see also p. 941