Design, synthesis, and characterization of piperazinedione-based dual protein inhibitors for both farnesyltransferase and geranylgeranyltransferase-I

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

13 Scopus Citations
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Author(s)

  • Yuqin Qiao
  • Jinbo Gao
  • Yongge Qiu
  • Long Wu
  • Fei Guo
  • Ding Li

Detail(s)

Original languageEnglish
Pages (from-to)2264-2273
Journal / PublicationEuropean Journal of Medicinal Chemistry
Volume46
Issue number6
Publication statusPublished - Jun 2011

Abstract

Farnesyltransferase (FTase) and geranylgeranyltransferase type-I (GGTase-I) both catalyze the prenylation of protein substrate containing a typical -CAAX motif at the carboxyl terminus. The inhibitors for these two enzymes have been widely studied as potential cancer chemotherapeutic agents. In the present study, various piperazinedione derivatives were designed and synthesized as a new type of peptide mimetic compounds, which were characterized and found to be dual protein inhibitors for both FTase and GGTase-I. These compounds have similar chemical and physical properties to -CAAX motif of the protein substrate, which may facilitate their transfer to appropriate drug target in vivo. The best inhibitor compound 26b was found to occupy both isoprenoid and peptide substrate binding sites through kinetics and computer molecular docking studies. © 2011 Elsevier Masson SAS.

Research Area(s)

  • Cancer, Dual protein inhibitor, Farnesyltransferase, Geranylgeranyltransferase, Piperazinedione

Citation Format(s)

Design, synthesis, and characterization of piperazinedione-based dual protein inhibitors for both farnesyltransferase and geranylgeranyltransferase-I. / Qiao, Yuqin; Gao, Jinbo; Qiu, Yongge; Wu, Long; Guo, Fei; Kam-Wing Lo, Kenneth; Li, Ding.

In: European Journal of Medicinal Chemistry, Vol. 46, No. 6, 06.2011, p. 2264-2273.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal