Molecular Mechanism of Food-Derived Polyphenols on PD-L1 Dimerization: A Molecular Dynamics Simulation Study

In cancer immunotherapy, an emerging approach is to block the interactions of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) using small-molecule inhibitors. The food-derived polyphenols curcumin (CC), resveratrol (RSV) and epigallocatechin gallate (EGCG) have anticancer immunologic functions, which, recently, have been proposed to act via the downregulation of PD-L1 expression. However, it remains unclear whether they can directly target PD-L1 dimerization and, thus, interrupt the PD-1/PD-L1 pathway. To elucidate the molecular mechanism of such compounds on PD-L1 dimerization, molecular docking and nanosecond molecular dynamics simulations were performed. Binding free energy calculations show that the affinities of CC, RSV and EGCG to the PD-L1 dimer follow a trend of CC > RSV > EGCG. Hence, CC is the most effective inhibitor of the PD-1/PD-L1 pathway. Analysis on contact numbers, nonbonded interactions and residue energy decomposition indicate that such compounds mainly interact with the C-, F- and G-sheet fragments of the PD-L1 dimer, which are involved in interactions with PD-1. More importantly, nonpolar interactions between these compounds and the key residues Ile54, Tyr56, Met115, Ala121 and Tyr123 play a dominant role in binding. Free energy landscape and secondary structure analyses further demonstrate that such compounds can stably interact with the binding domain of the PD-L1 dimer. The results provide evidence that CC, RSV and EGCG can inhibit PD-1/PD-L1 interactions by directly targeting PD-L1 dimerization. This provides a novel approach to discovering food-derived small-molecule inhibitors of the PD-1/PD-L1 pathway with potential applications in cancer immunotherapy.     

食物蛋白源免疫调节肽研究进展

免疫系统在维持人类健康方面发挥重要作用,免疫系统功能失调或受损会引发疾病。目前常用的调节免疫功能的化学药物存在价格昂贵、毒副作用大等缺点,因此开发高效、安全的免疫调节制剂成为研究热点。食物蛋白源免疫调节肽是利用食源性蛋白获得的具有调节免疫功能的多肽,其免疫调节活性与氨基酸组成、序列及肽链长度有关。文章综述了近年来食物蛋白源免疫调节活性肽的类型、获取途径、功效评价方法及作用机制,旨在为免疫调节相关的功能性食品或药物的研究及开发提供参考。     

食物源蛋白酶解制备抗菌肽研究

抗菌肽广泛分布于细菌、病毒和各种动植物体内,是生物天然免疫防御系统的重要组成部分。在耐药菌株不断产生的今天,抗菌肽的研究吸引着国内外学者目光。本文综述了乳源蛋白和非乳源蛋白酶解制备抗菌肽、酶解作用提高抗菌蛋白的抗菌性、酶及酶解条件的选择、抗菌产物目的性修饰提高抗菌性的研究,并展望了食物源蛋白酶解制备抗菌肽的未来研究方向。     

食源性肽研究进展

食源性肽是以食用蛋白为原料,经过酶解、分离、纯化等制成的新型蛋白水解产品.阐述了食源性肽的营养保健功能和生产方法、食源性肽类产品的评价、认可情况及质量标准的研究现状,并对含有生物活性肽的传统食品以及已商业化的食源性肽类终端食品进行了概述和总结,最后对其应用前景进行了展望.     

食源性生物活性肽对2型糖尿病的干预作用及其机制研究进展

2型糖尿病属于非胰岛素依赖性糖尿病,全世界每年有数百万人患2型糖尿病或成为潜在患者。食源性活性肽不仅具有基本的营养优势,而且更易被机体吸收,有研究证实生物活性肽可以抑制与2型糖尿病相关的代谢酶活力,促进肠促胰岛素分泌,改善胰岛素抵抗,因此可以作为有效管理该疾病的功能性食品或药物。本文综述了食源性生物活性肽的特性和来源,以及目前其关于调节血糖作用机制的研究进展,归纳了食源性代谢酶调节剂的相关研究,以期为食源性生物活性肽的进一步研究提供参考。     

食源性肽的功能特性评价方法、分子构效关系及吸收代谢机制

肽是分子结构介于氨基酸和蛋白质之间的化合物,具有易吸收、低渗透压、低免疫原性、高组织渗透性等营养特性,可调控细胞代谢,是组织细胞的重要化学信使。食源性肽是食物蛋白质经限制性酶解法或生物发酵法等制备的重要营养基料,兼具良好的营养价值和多种生理调节活性。但目前食源性肽转运吸收过程、胞内亚细胞器时空动态分布以及营养代谢调控功能尚待研究,且不同结构和功能的肽分子(跨膜肽、信号肽、转运肽等)间协同作用模式也未明晰,严重制约了食源性肽的基础研究与产业快速发展。系统介绍了以化学、体外生物、低等/高等模式动物以及临床等多维度的肽功能评价方法;解析了食源性肽的分子构效关系,以“自上而下”与“自下而上”的2种方式分别阐述了食源性肽的分子构效规律分析方法,并创新了基于分子杂化轨道的“结构-功效”表征理论;揭示了不同分子结构特征(一级氨基酸序列、空间构型、主链肽键的排列方式、侧链官能团的多样化及α-碳的手性等)的肽分子在转运吸收过程中的构效关系;进一步探讨了营养研究领域中复杂体系下食源性蛋白肽吸收及调控机体代谢的规律,深度挖掘肽吸收代谢与营养的科学基础,对基于食源性肽开展精准营养调控具有重要借鉴意义。对食源性肽的功能特性评价方法、“构-效”关系和吸收代谢机理进行了系统的阐述,以期为未来食源性肽的研究提供科学的指导和参考。     

不同取材的食源性低聚肽嘌呤含量测定及其在痛风患者营养治疗中的应用探讨

利用高效液相色谱法对7种不同取材的食源性低聚肽样品进行嘌呤含量检测,检测结果由低到高分别为玉米蛋白低聚肽、乳清蛋白低聚肽、卵白蛋白低聚肽、大豆蛋白低聚肽、海洋蛋白低聚肽、海洋胶原低聚肽以及海洋骨原低聚肽。其中前3种为低嘌呤食物,后2种为高嘌呤食物,中间的2种为中嘌呤食物。这与各自取材原料的食品嘌呤等级相一致。鉴于上述低嘌呤肽达到低嘌呤食品的要求,结合肽自身的生理功能,探讨其在痛风患者营养治疗中的应用,认为低嘌呤肽可作为优质的蛋白补充源,缓解痛风患者的合并症,促进尿酸的排泄。     

Protective effects of orally administered shark compound peptides from Chiloscyllium plagiosum against acute inflammation

The anti-inflammatory effects of shark compound peptides (SCP) from Chiloscyllium plagiosum were investigated. Results showed that SCP enhanced the viability of RAW 264.7 macrophages in vitro in a dose-dependent manner. Orally administered SCP exhibited potent anti-inflammatory activity in lipopolysaccharide (LPS)-challenged mice by suppressing serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), as well as nitric oxide (NO). Moreover, SCP significantly inhibited the inflammatory rise of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatinine (CRE), while blocking the decline of cholinesterase (CHE), with an efficacy close to aspirin. This research showed that orally administered SCP from C. plagiosum notably downregulated uncontrolled inflammatory responses, and conferred substantial protection from endotoxin-induced acute hepatic damage and renal functional impairment. Therefore, oral supplementation of SCP can be used as a preventive approach to reduce the risk of inflammatory-related diseases.     

An updated review on food-derived bioactive peptides: Focus on the regulatory requirements,safety, and bioavailability

Food-derived bioactive peptides (BAPs) are recently utilized as functional food raw materials owing to their potential health benefits. Although there is a huge amount of scientific research about BAPs’ identification, purification, characterization, and physiological functions, and subsequently, many BAPs have been marketed, there is a paucity of review on the regulatory requirements, bioavailability, and safety of BAPs. Thus, this review focuses on the toxic peptides that could arise from their primary proteins throughout protein extraction, protein pretreatment, and BAPs’ formulation. Also, the influences of BAPs’ length and administration dosage on safety are summarized. Lastly, the challenges and possibilities in BAPs’ bioavailability and regulatory requirements in different countries were also presented. Results revealed that the human studies of BAPs are essential for approvals as healthy food and to prevent the consumers from misinformation and false promises. The BAPs that escape the gastrointestinal tract epithelium and move to the stomach are considered good peptides and get circulated into the blood using different pathways. In addition, the hydrophobicity, net charge, molecular size, length, amino acids composition/sequences, and structural characteristics of BAPs are critical for bioavailability, and appropriate food-grade carriers can enhance it. The abovementioned features are also vital to optimize the solubility, water holding capacity, emulsifying ability, and foaming property of BAPs in food products. In the case of safety, the possible allergenic and toxic peptides often exhibit physiological functions and could be produced during the hydrolysis of food proteins. It was also noted that the production of iso-peptides bonds and undesirable Maillard reaction might occur during protein extraction, sample pretreatments, and peptide synthesis.