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Related Concept Videos

Production of Pharmaceuticals01:30

Production of Pharmaceuticals

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Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under...
100

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Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies
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Bioproduction Platform to Generate Functionalized Disulfide-Constrained Peptide Analogues.

Sunhee Hwang1, Aaron T Balana1, Bryan Martin2

  • 1Department of Peptide Therapeutics, Genentech Incorporated, South San Francisco, California 94080, United States.

ACS Bio & Med Chem Au
|August 26, 2024
PubMed
Summary
This summary is machine-generated.

This study introduces a sustainable bioproduction platform for disulfide-constrained peptides (DCPs), offering a cost-effective and eco-friendly alternative to chemical synthesis for drug development.

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Area of Science:

  • Biotechnology
  • Chemical Biology
  • Drug Discovery

Background:

  • Disulfide-constrained peptides (DCPs) are a promising drug modality, combining benefits of biologics and small molecules.
  • Current chemical synthesis methods for DCPs are costly and environmentally burdensome.

Purpose of the Study:

  • To develop a versatile, low-cost, and environmentally friendly bioproduction platform for DCPs and their conjugates.
  • To demonstrate the feasibility of producing chemically modified and isotope-labeled DCPs via bioproduction.

Main Methods:

  • Bacterial expression of DCPs, utilizing Ser ligation or transglutaminase-mediated XTEN ligation.
  • Amber codon suppression system for site-specific incorporation of unnatural amino acids.
  • Production of 15N/13C-labeled DCPs and assessment of a semiautomated resonance assignment workflow.

Main Results:

  • Successful production of multivalent DCPs and DCPs with N-terminal functional groups using bacterial expression and ligation strategies.
  • Demonstrated site-specific incorporation of unnatural amino acids into recombinant DCPs.
  • High yield production of isotope-labeled DCPs and validation of an accelerated resonance assignment workflow.

Conclusions:

  • Bioproduction offers a sustainable, cost-effective, and efficient alternative to chemical synthesis for DCP generation.
  • This platform enables the creation of functionalized DCPs, expediting drug discovery and characterization.
  • The developed methods reduce reliance on hazardous chemicals and lower production costs.