1. [New non-peptide inhibitors of furin]
V K Kibirev, T V Osadchuk, O B Vadziuk, M M Garazd Ukr Biokhim Zh (1999). 2010 Mar-Apr;82(2):15-21.
Furin, a human subtilisin-related proprotein convertase, is the most important pharmaceutical target because it plays a vital role in development of numerous disease processes. To identify a new class of small non-peptide inhibitors of furin we performed a study of several flavonoids and some natural products. Glycosylated flavonoids: rutin, naringin, baikalin and methylhesperidin were shown to inhibit furin at pH 7.2 reversibly and competitively with Ki- 80-200 microM. The Ki values were derived from Dixon and/or Eadie-Hofstee plots using fluorogenic substrate Boc-Arg-Val-Arg-Arg-AMC. Although studied flavonoids display only a temperate furin inhibition, they may serve as a great potential for the future development of more potent non-peptide inhibitors against furin.
2. Internally quenched fluorogenic substrate for furin
H Angliker, U Neumann, S S Molloy, G Thomas Anal Biochem. 1995 Jan 1;224(1):409-12. doi: 10.1006/abio.1995.1058.
A new substrate for furin, Abz-Arg-Val-Lys-Arg-Gly-Leu-Ala-Tyr(NO2)-Asp-OH, has been synthesized and characterized. The peptide is an internally quenched fluorogenic substrate. The kinetic parameters are Km = 3.8 microM, kcat = 29.3 s-1, and kcat/KM = 7,710,000 M-1 s-1. The substrate is efficiently cleaved by furin; its kcat/KM value is over 2000-fold higher than that of the commonly used substrate Boc-Arg-Val-Arg-Arg-AMC.
