Relieving the first bottleneck in the drug discovery pipeline: using array technologies to rationalize membrane protein production

Nicklas Bonander, Roslyn M. Bill

Research output: Contribution to journalArticle

Abstract

The slow down in the drug discovery pipeline is, in part, owing to a lack of structural and functional information available for new drug targets. Membrane proteins, the targets of well over 50% of marketed pharmaceuticals, present a particular challenge. As they are not naturally abundant, they must be produced recombinantly for the structural biology that is a prerequisite to structure-based drug design. Unfortunately, however, obtaining high yields of functional, recombinant membrane proteins remains a major bottleneck in contemporary bioscience. While repeated rounds of trial-and-error optimization have not (and cannot) reveal mechanistic details of the biology of recombinant protein production, examination of the host response has provided new insights. To this end, we published an early transcriptome analysis that identified genes implicated in high-yielding yeast cell factories, which has enabled the engineering of improved production strains. These advances offer hope that the bottleneck of membrane protein production can be relieved rationally.
Original languageEnglish
Pages (from-to)501-505
Number of pages5
JournalExpert Review of Proteomics
Volume6
Issue number5
DOIs
Publication statusPublished - Oct 2009

Bibliographical note

Reproduced from Expert Review of Proteomics, October 2009, Vol. 6, No. 5, Pages 501-505 with permission of Expert Reviews Ltd.

Keywords

  • drug discovery
  • membrane proteins
  • polymerase chain reaction
  • recombinant Proteins
  • saccharomyces cerevisiae

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