Expedient solid-phase synthesis of fluorogenic protease substrates using the 7-amino-4-carbamoylmethylcoumarin (ACC) fluorophore

J Org Chem. 2002 Feb 8;67(3):910-5. doi: 10.1021/jo016140o.


A highly efficient solid-phase synthesis method for the preparation of fluorogenic protease substrates based upon the bifunctional leaving group 7-amino-4-carbamoylmethylcoumarin (ACC) is reported. Methods for the large-scale preparation of the novel fluorogenic leaving-group ACC are provided (Scheme 1). Detailed procedures are also provided for loading a diverse set of amino acids to support-bound ACC in good yields and with minimal racemization. Finally, procedures are included for the preparative synthesis of optimized ACC substrates for HIV-1 protease and plasmin.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / chemistry
  • Coumarins / chemistry
  • Coumarins / metabolism*
  • Fibrinolysin / metabolism*
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism*
  • HIV Protease / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Substrate Specificity


  • 7-amino-4-carbamoylmethylcoumarin
  • Amino Acids
  • Coumarins
  • Fluorescent Dyes
  • Fibrinolysin
  • HIV Protease