Engineering Research Center of Bio-process, Ministry of Education, School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China.
Department of Food Science and Human Nutrition, Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 228 Edward R. Madigan Laboratory (ERML), 1201 West Gregory Drive, Urbana, Illinois 61801, USA.
Food Funct. 2022 May 10;13(9):5215-5228. doi: 10.1039/d1fo04367f.
The potential of pentapeptide IPQVS (RAP1) and octapeptide ELHQEEPL (RAP2) derived from rapeseed napin as natural dipeptidyl-peptidase IV (DPP-IV) inhibitors is promising. The objective was to develop a nanogel strategy to resist the hydrolysis of digestive and intestinal enzymes to enhance the DPP-IV inhibitory activity of RAP1 and RAP2, and stimulate glucagon-like peptide 1 (GLP-1) secretion of RAP2 by a RADA16-assisted molecular design. The linker of double Gly was used in the connection of RADA16 and the functional oligopeptide region (RAP1 and RAP2). Compared to the original oligopeptides, DPP-IV IC of the nanogels RADA16-RAP1 and RADA16-RAP2 decreased by 26.43% and 17.46% in Caco-2 cell monolayers, respectively. The results showed that the two nanogel peptides with no toxicity to cells had higher contents of stable β-sheet structures (increased by 5.6-fold and 5.2-fold, respectively) than the original oligopeptides, and a self-assembled fibrous morphology. Rheological results suggested that the nanogels RADA16-RAP1 and RADA16-RAP2 exhibit good rheological properties for potential injectable applications; the storage modulus (') was 10 times higher than the low modulus (''). Furthermore, the RAP2 and its RADA16-assisted nanogel peptide at the concentration of 250 μM significantly ( < 0.05) increased the release of GLP-1 by 35.46% through the calcium-sensing receptor pathway in the enteroendocrine STC-1 cells. Hence, the innovative and harmless nanogels with the sequence of RADA16-GG-X have the potential for use by oral and injection administration for treating or relieving type 2 diabetes.
菜籽油中 napin 衍生的五肽 IPQVS（RAP1）和八肽 ELHQEEPL（RAP2）作为天然二肽基肽酶 IV（DPP-IV）抑制剂具有很大的潜力。本研究旨在开发纳米凝胶策略来抵抗消化和肠道酶的水解，以增强 RAP1 和 RAP2 的 DPP-IV 抑制活性，并通过 RADA16 辅助的分子设计刺激 RAP2 分泌胰高血糖素样肽 1（GLP-1）。双甘氨酸接头用于 RADA16 与功能性寡肽区域（RAP1 和 RAP2）的连接。与原始寡肽相比，纳米凝胶 RADA16-RAP1 和 RADA16-RAP2 在 Caco-2 细胞单层中的 DPP-IV IC 分别降低了 26.43%和 17.46%。结果表明，这两种对细胞无毒的纳米凝胶肽具有比原始寡肽更高的稳定β-折叠结构含量（分别增加了 5.6 倍和 5.2 倍），并且具有自组装的纤维形态。流变学结果表明，纳米凝胶 RADA16-RAP1 和 RADA16-RAP2 具有良好的流变性能，适用于潜在的可注射应用；储能模量（'）比低模量（'）高 10 倍。此外，浓度为 250 μM 的 RAP2 及其 RADA16 辅助纳米凝胶肽通过肠内分泌 STC-1 细胞中的钙敏感受体途径显著（<0.05）增加了 35.46%的 GLP-1 释放。因此，具有 RADA16-GG-X 序列的创新且无害的纳米凝胶具有通过口服和注射给药用于治疗或缓解 2 型糖尿病的潜力。
