Rapid Flow-Based Peptide Synthesis
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Pentelute_Rapid flow.pdf
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793.06 KB
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Author(s)
Heider, Patrick L.
Adamo, Andrea
Vinogradov, Alexander A.
Li, Xiyuan
Berger, Tatiana
Policarpo, Rocco L.
Zhang, Chi
Zou, Yekui
Liao, Xiaoli
Spokoyny, Alexander M.
Date Issued
March 2014
Journal
ChemBioChem
Publisher
Wiley Blackwell
Citation
Simon, Mark D., Patrick L. Heider, Andrea Adamo, Alexander A. Vinogradov, Surin K. Mong, Xiyuan Li, Tatiana Berger, et al. “Rapid Flow-Based Peptide Synthesis.” ChemBioChem 15, no. 5 (March 11, 2014): 713–720.
Version
Author's final manuscript
Abstract
A flow-based solid-phase peptide synthesis methodology that enables the incorporation of an amino acid residue every 1.8 min under automatic control or every 3 min under manual control is described. This is accomplished by passing a stream of reagent through a heat exchanger into a low volume, low backpressure reaction vessel, and through a UV detector. These features enable continuous delivery of heated solvents and reagents to the solid support at high flow rate, thereby maintaining maximal concentration of reagents in the reaction vessel, quickly exchanging reagents, and eliminating the need to rapidly heat reagents after they have been added to the vessel. The UV detector enables continuous monitoring of the process. To demonstrate the broad applicability and reliability of this method, it was employed in the total synthesis of a small protein, as well as dozens of peptides. The quality of the material obtained with this method is comparable to that for traditional batch methods, and, in all cases, the desired material was readily purifiable by RP-HPLC. The application of this method to the synthesis of the 113-residue Bacillus amyloliquefaciens RNase and the 130-residue DARPin pE59 is described in the accompanying manuscript.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1002/cbic.201300796
