Kuntz D A, Osowski R, Schudok M, Wierenga R K, Müller K, Kessler H, Opperdoes F R
Research Unit for Tropical Diseases, International Institute of Molecular Pathology, Brussels, Belgium.
Eur J Biochem. 1992 Jul 15;207(2):441-7. doi: 10.1111/j.1432-1033.1992.tb17069.x.
Two series of oligopeptides have been synthesized. Their effects on the activity of purified triosephosphate isomerase from Trypanosoma brucei and various other organisms have been studied. Using detailed three-dimensional structure information, the first series consisted of both cyclic and linear hydrophilic peptides that were designed to mimic the beta turns of the subunit interface loops of the trypanosome triosephosphate isomerase dimer. None of these exerted any inhibitory effect. The second series consisted of more hydrophobic cyclic peptides, originally designed to inhibit a hepatic transport system. Several of these were very effective in inhibiting the trypanosome triosephosphate isomerase, but not the homologous enzymes from rabbit, dog, yeast or Escherichia coli. The most active peptide, cyclo[-Trp-Phe-D-Pro-Phe-Phe-Lys(Z)-], exerted 50% inhibitory activity at a concentration of 3 microM. The nature of the inhibitory action of one of these compounds cyclo[-Trp-Tyr(OSO3Na)-D-Pro-Phe-Thr(OSO3Na)-Lys(Z)-] was studied in more detail. Its inhibition was noncompetitive and reversible and more than one peptide was able to bind/active site.
已经合成了两个系列的寡肽。研究了它们对来自布氏锥虫和其他各种生物体的纯化磷酸丙糖异构酶活性的影响。利用详细的三维结构信息，第一个系列由环状和亲水性线性肽组成，这些肽被设计用来模拟锥虫磷酸丙糖异构酶二聚体亚基界面环的β转角。这些肽均未产生任何抑制作用。第二个系列由更多的疏水性环状肽组成，最初设计用于抑制肝脏转运系统。其中几种肽对锥虫磷酸丙糖异构酶具有非常有效的抑制作用，但对来自兔、犬、酵母或大肠杆菌的同源酶没有抑制作用。活性最高的肽环[ - 色氨酸 - 苯丙氨酸 - D - 脯氨酸 - 苯丙氨酸 - 苯丙氨酸 - 赖氨酸（Z）- ]在浓度为3 microM时表现出50%的抑制活性。对其中一种化合物环[ - 色氨酸 - 酪氨酸（OSO3Na）- D - 脯氨酸 - 苯丙氨酸 - 苏氨酸（OSO3Na）- 赖氨酸（Z）- ]的抑制作用性质进行了更详细的研究。其抑制作用是非竞争性的且可逆的，并且不止一种肽能够结合/活性位点。
