Center for Membrane and Film Technology, Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan.
Department of Applied Chemistry, Faculty of Engineering, University of Miyazaki, 1-1 Gakuen Kibanadai Nishi, Miyazaki 889-2192, Japan.
Colloids Surf B Biointerfaces. 2018 Jul 1;167:144-149. doi: 10.1016/j.colsurfb.2018.03.040. Epub 2018 Mar 29.
Recently, digestive peptides prepared as a casein hydrolysate have been found to be an effective dispersant for the poorly water-soluble drug paclitaxel (Ptx). A major hydrophobic peptide in the digested peptides was identified as YQEPVLGPVRGPFPIIV (PepY) by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry with the "LIFT" technique. In the present study, three peptides PepY, VVVPPFLQPEVMGVSKV (PepV), and KFQSEEQQQTEDELQDK (PepK) were chemically synthesized by Fmoc solid-phase synthesis to compare their function as dispersants for Ptx. PepV and PepK are the most hydrophobic and hydrophilic peptides, respectively, in the sequence of β-casein, which are the same length as PepY (PepY, PepV, and PepK are abbreviated as Peps). The complex between Ptx and Peps (Ptx-Peps) was prepared by mixing an ethanol solution of Ptx and an aqueous solution of Peps, followed by lyophilization. The complex with PepV, which is estimated to be the most hydrophobic of the peptides, had the greatest ability to improve the water dispersibility of Ptx. The water dispersibility of the complexes between Ptx and PepY and PepV increased as the amount of the peptides increased, whereas PepK was not effective in enhancing the dispersibility of Ptx. Furthermore, a peptide mixture obtained from a casein hydrolysate [Pep (fraction A)] was more effective for the enhancement of Ptx dispersibility than the single peptide PepY. These results suggests that a variety of peptides in the casein hydrolysate contribute toward complexation with Ptx.
最近，作为酪蛋白水解产物制备的消化肽已被发现是一种有效分散剂，可用于提高疏水性药物紫杉醇（Ptx）的水溶性。通过基质辅助激光解吸/电离飞行时间/飞行时间质谱联用“LIFT”技术，鉴定出消化肽中的主要疏水性肽为 YQEPVLGPVRGPFPIIV（PepY）。在本研究中，通过 Fmoc 固相合成法化学合成了三种肽 PepY、VVVPPFLQPEVMGVSKV（PepV）和 KFQSEEQQQTEDELQDK（PepK），以比较它们作为 Ptx 分散剂的功能。PepV 和 PepK 是 β-酪蛋白序列中疏水性最强和最亲水性的肽，长度与 PepY 相同（PepY、PepV 和 PepK 缩写为 Peps）。通过将 Ptx 的乙醇溶液与 Peps 的水溶液混合，然后冻干，制备 Ptx 与 Peps 的复合物（Ptx-Peps）。与估计是肽中疏水性最强的 PepV 形成的复合物具有最大提高 Ptx 水分散性的能力。Ptx 与 PepY 和 PepV 之间的复合物的水分散性随着肽量的增加而增加，而 PepK 则不能有效提高 Ptx 的分散性。此外，从酪蛋白水解物中获得的肽混合物（Pep（A 部分））比单一肽 PepY 更有效地提高 Ptx 的分散性。这些结果表明，酪蛋白水解物中的多种肽有助于与 Ptx 形成复合物。
