Solid-phase peptide synthesis under continuous-flow conditions.

T. J. Lukas, M. B. Prystowsky, B. W. Erickson

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44 Scopus citations


A system is described for solid-phase synthesis of peptides under continuous-flow conditions with liquid chromatographic equipment, conventional polystyrene supports, and well-defined chemistry. The model tetrapeptide Leu-Ala-Gly-Val was assembled in 99.3% purity in about 4 hr on microporous copoly(styrene-1% divinylbenzene). During coupling, the preformed symmetric anhydrides were conserved by being recycled. Relative yields of the peptide products were determined quantitatively in 20 min by reverse-phase high-pressure liquid chromatography. This rapid assay system was used to examine the influence on product yields of (i) the time and number of couplings per cycle, (ii) microporous versus macroporous polystyrene, and (iii) tert-butoxycarbonyl (Boc) group versus 9-fluorenylmethoxycarbonyl for amine protection. Use of microporous polystyrene and two 30-min couplings of Boc-amino acids per cycle gave the best results. This continuous-flow system provides a rapid and efficient approach to solid-phase peptide synthesis. A 17-residue peptide from chicken ovalbumin was obtained in similar purity and yield from a discontinuous synthesis and from a continuous-flow synthesis.

Original languageEnglish (US)
Pages (from-to)2791-2795
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - May 1981
Externally publishedYes

ASJC Scopus subject areas

  • General


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