Synthesis and evaluation of photolabile insulin prodrugs

Lian Sheng Li, Jennie L. Babendure, Subhash C. Sinha, Jerrold M. Olefsky, Richard A. Lerner

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

We have developed two photolabile insulin prodrugs, insulin-2P and insulin-3P. These prodrugs were synthesized by protecting GlyA1 (N αA1), and one or both of the PheB1 (NαB1) and LysB29 (NεB29) amino groups in insulin using 5′-(α-methyl-nitro-piperonyl)oxy-carbonyl as the protecting group. These insulin prodrugs were efficiently activated by exposure to longwave UV light to produce insulin quantitatively. Using 2-deoxyglucose uptake assays, both di- and tri-protected compounds were less active than native insulin in the protected state, and showed comparable activity to native insulin upon photoactivation.

Original languageEnglish (US)
Pages (from-to)3917-3920
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number17
DOIs
StatePublished - Sep 1 2005

Keywords

  • Diabetes
  • Insulin
  • Photolysis
  • Prodrug
  • Ultraviolet

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Li, L. S., Babendure, J. L., Sinha, S. C., Olefsky, J. M., & Lerner, R. A. (2005). Synthesis and evaluation of photolabile insulin prodrugs. Bioorganic and Medicinal Chemistry Letters, 15(17), 3917-3920. https://doi.org/10.1016/j.bmcl.2005.05.112