Lacroix Isabelle M E, Li-Chan Eunice C Y
The University of British Columbia, Faculty of Land & Food Systems, Food Nutrition & Health Program, 2205 East Mall, Vancouver, BC, Canada V6T 1Z4.
The University of British Columbia, Faculty of Land & Food Systems, Food Nutrition & Health Program, 2205 East Mall, Vancouver, BC, Canada V6T 1Z4.
Peptides. 2014 Apr;54:39-48. doi: 10.1016/j.peptides.2014.01.002. Epub 2014 Jan 17.
Inhibition of the enzyme dipeptidyl peptidase (DPP)-IV is one of the strategies used for the treatment of type 2 diabetes. In the present study, pepsin-treated whey protein isolate (WPI) and α-lactalbumin displaying DPP-IV inhibitory activity were fractionated by successive chromatographic steps and the resulting active fractions analyzed for their constituent peptides by liquid chromatography-electrospray ionization-tandem mass spectrometry. Among the identified sequences, 24 peptides derived from α-lactalbumin and 11 from β-lactoglobulin were synthesized and their effects on DPP-IV activity assessed. The most potent fragments, LKPTPEGDL and LKPTPEGDLEIL (IC50=45 and 57 μM, respectively), were found to inhibit DPP-IV in an un-competitive manner. Although several of the peptides tested showed some inhibitory activity, only two were as effective as the un-fractionated WPI hydrolysate and none were as potent as the un-fractionated α-lactalbumin hydrolysate. The peptides' structural features, including length and amino acid composition, were found to impact their inhibitory activity. This study provides new insights on the active components responsible for the DPP-IV inhibitory activity of pepsin-treated whey proteins.
抑制二肽基肽酶（DPP）-IV是用于治疗2型糖尿病的策略之一。在本研究中，用胃蛋白酶处理的乳清蛋白分离物（WPI）和具有DPP-IV抑制活性的α-乳白蛋白通过连续的色谱步骤进行分级分离，并用液相色谱-电喷雾电离-串联质谱法分析所得活性级分的组成肽。在鉴定出的序列中，合成了24个源自α-乳白蛋白的肽和11个源自β-乳球蛋白的肽，并评估了它们对DPP-IV活性的影响。发现最有效的片段LKPTPEGDL和LKPTPEGDLEIL（IC50分别为45和57μM）以非竞争性方式抑制DPP-IV。尽管测试的几种肽显示出一定的抑制活性，但只有两种与未分级的WPI水解产物一样有效，且没有一种与未分级的α-乳白蛋白水解产物一样有效。发现肽的结构特征，包括长度和氨基酸组成，会影响它们的抑制活性。本研究为胃蛋白酶处理的乳清蛋白中负责DPP-IV抑制活性的活性成分提供了新的见解。
