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Large-scale manufacture of peptide therapeutics by chemical synthesis

Nature Reviews Drug Discovery volume 2, pages 587–593 (2003)Cite this article

Abstract

The large-scale commercial production of a 36-amino-acid peptide by chemical synthesis has been demonstrated in the development of enfuvirtide (T-20 or Fuzeon), a first-in-class membrane fusion inhibitor for the treatment of HIV. The rationale behind route selection and the scale-up of the process used to manufacture enfuvirtide are discussed.

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Figure 1: Linear solid-phase peptide synthesis using Fmoc-protected amino acids.
Figure 2: Solid-phase synthesis of a protected peptide fragment using Fmoc-protected amino acids and a super acid-sensitive resin.
Figure 3: Route 2 synthesis of T-2O.
Figure 4: Sequence failures during solid-phase peptide synthesis leading to single-site deletions, double hits or diastereomers.

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  1. Trimeris, Inc., 3518 West Gate Drive, Durham, NC27707, Noth Carolina, USA

    Brian L. Bray

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  1. Brian L. Bray
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FURTHER INFORMATION

Encyclopedia of Life Sciences

Robert Bruce Merrifield

Enfuvirtide mechanism of action

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Bray, B. Large-scale manufacture of peptide therapeutics by chemical synthesis. Nat Rev Drug Discov 2, 587–593 (2003). https://doi.org/10.1038/nrd1133

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