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

被引:123
作者
Maly, DJ
Leonetti, F
Backes, BJ
Dauber, DS
Harris, JL
Craik, CS
Ellman, JA [1 ]
机构
[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[2] Univ Calif San Francisco, Dept Pharmaceut Chem, Program Chem & Chem Biol, San Francisco, CA 94143 USA
关键词
D O I
10.1021/jo016140o
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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.
引用
收藏
页码:910 / 915
页数:6
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