Synthesis and Characterization of an A6-A11 Methylene Thioacetal Human Insulin Analogue with Enhanced Stability

J Med Chem. 2019 Dec 26;62(24):11437-11443. doi: 10.1021/acs.jmedchem.9b01589. Epub 2019 Dec 13.


Insulin has been a life-saving drug for millions of people with diabetes. However, several challenges exist which limit therapeutic benefits and reduce patient convenience. One key challenge is the fibrillation propensity, which necessitates refrigeration for storage. To address this limitation, we chemically synthesized and evaluated a methylene thioacetal human insulin analogue (SCS-Ins). The synthesized SCS-Ins showed enhanced serum stability and aggregation resistance while retaining bioactivity compared with native insulin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Disulfides / chemistry*
  • Disulfides / metabolism
  • Drug Design*
  • Drug Stability
  • Female
  • Humans
  • Insulin / chemistry*
  • Insulin / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Protein Conformation
  • Sulfhydryl Compounds / chemistry*


  • Disulfides
  • Insulin
  • Peptide Fragments
  • Sulfhydryl Compounds