Chemoenzymatic synthesis and high-throughput screening of an aminoglycoside-polyamine library: Identification of high-affinity displacers and DNA-binding ligands

Kaushal Rege, Shanghui Hu, James A. Moore, Jonathan S. Dordick, Steven M. Cramer

Research output: Contribution to journalArticle

39 Scopus citations


Chemoenzymatic parallel synthesis and high-throughput screening were employed to develop a multivalent aminoglycoside-polyamine library for use as high-affinity cation-exchange displacers and DNA-binding ligands. Regioselective lipase-catalyzed acylation, followed by chemical aminolysis, was used to generate vinyl carbonate and vinyl carbamate linkers, respectively, of the aminoglycosidic cores. These were further derivatized with polyamines, leading to library generation. A parallel batch-displacement assay was employed to identify the efficacy of the library candidates as potential displacers for protein purification. Using this approach, low-molecular-mass displacers with affinities higher than those previously observed have been identified. The aminoglycoside-polyamine library was also screened for DNA binding efficacy using an ethidium bromide displacement assay. These highly cationic molecules exhibited strong DNA-binding properties and may have potential for enhanced gene delivery.

Original languageEnglish (US)
Pages (from-to)12306-12315
Number of pages10
JournalJournal of the American Chemical Society
Issue number39
StatePublished - Oct 6 2004


ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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