Quantitative structure-activity relationship studies of acteylcholinesterase-inhibitory peptides
Quantitative structure-activity relationship studies of acteylcholinesterase-inhibitory peptides
批准号:
RGPIN-2018-06019
负责人:
Aluko, Rotimi
金额:
$3.42万
依托单位:
依托单位国家:
加拿大
项目类别:
Discovery Grants Program - Individual
财政年份:
2019
资助国家:
加拿大
项目状态:
已结题
起止时间:
2019-01-01 至 2020-12-31
中文摘要
生物活性肽是存在于食物蛋白质线性链中的短序列氨基酸(<20个残基),可以通过仔细的酶消化释放出来。释放后,这些肽成为潜在的强大的药物,可以恢复正常的生理过程。科学文献已经证实,氨基酸的线性排列是决定肽活性类型和效力的重要因素。因此,本提案的重点是确定影响乙酰胆碱酯酶(AChE)抑制肽效力的氨基酸位置排列。人乙酰胆碱酯酶是一种酯酶,可水解乙酰胆碱,乙酰胆碱是神经系统中的主要神经递质。乙酰胆碱酯酶的过度活动与神经系统紊乱有关,特别是痴呆和阿尔茨海默病。然而,关于氨基酸类型和肽链上的位置与抑制乙酰胆碱酯酶活性的关系的信息很少。我的国家科学研究委员会资助的发现研究项目的初步工作已经证明了利用酶消化从大麻籽蛋白中释放乙酰胆酸抑制肽的可行性。该提案旨在继续胃蛋白酶的工作,包括其他食物蛋白质(豌豆,油菜籽,亚麻籽,大豆,鹰嘴豆),并最终导致发现新的疼痛抑制肽。因此,本提案的主要目的是分离、纯化和确定这些植物蛋白酶解物中存在的乙酰胆碱抑制肽的氨基酸序列。靶肽是指含有10个或更少氨基酸的肽,因为它们的小尺寸增加了穿过血脑屏障(BBB)、进入大脑、与乙酰胆碱结合并减少乙酰胆碱过度分解的潜力。因此,水解产物将通过1 kDa的超滤膜过滤,并收集流过的液体(渗透液)并用于肽纯化。纯化后的肽段将采用液相色谱/串联质谱法鉴定氨基酸序列,并用于建立偏最小二乘(PLS)回归分析的数据库。PLS模型将用于发现新的疼痛抑制肽。在Wistar大鼠模型中,研究人员将评估抗乙酰胆碱酯酶最强的肽穿过血脑屏障和降低乙酰胆碱酯酶脑活性的能力。这项工作具有重要意义,因为结果将为乙酰胆酸抑制肽的氨基酸结构需求提供基础科学信息。这些结构信息将有助于开发基于肽的营养工具,使与神经系统相关的生理障碍正常化。该项目为期5年,将培养3名博士后、2名博士、3名硕士和5名本科生暑期研究生。
英文摘要
Bioactive peptides are short sequences (<20 residues) of amino acids present within the linear chain of food proteins and can be released through careful enzymatic digestion. Upon release, these peptides become potentially powerful agents that can restore normal physiological processes. It has been established in scientific literature that the linear arrangement of amino acids is an important determinant of the type and potency of activity of the peptide. Therefore, the focus of this proposal is to determine the amino acid positional arrangements that influence potency of acetylcholinesterase (AChE)-inhibitory peptides. Human AChE is an esterase that hydrolyzes acetylcholine, the main neurotransmitter in the nervous system. Excessive activities of AChE have been implicated in disorders of the nervous system, especially dementia and Alzheimer's disease. However, there is scant information on the relationships of amino acid type and position on the peptide chain with ability to inhibit AChE activity. Preliminary work from my NSERC-funded Discovery research program has demonstrated the feasibility of using enzyme digestion to release AChE-inhibitory peptides from hemp seed proteins. This proposal seeks to continue the pepsin work to include other other food proteins (peas, canola, flaxseed, soybean, chickpea) and ultimately lead to the discovery of novel AChE-inhibitory peptides. Therefore, the main objectives of this proposal are to fractionate, purify, and determine the amino sequence of AChE-inhibitory peptides present in the enzymatic hydrolysates of these plant proteins. Target peptides are those with 10 or less amino acids because their small sizes increase the potential to cross the blood-brain barrier (BBB), enter the brain, bind to AChE and reduce excessive breakdown of acetylcholine. Thus, the hydrolysates will be filtered through a 1 kDa ultrafiltration membrane and the flow-through (permeate) collected and used for peptide purification. Purified peptides will be subjected to liquid chromatography/tandem mass spectrometry to identify amino acid sequences, which will be used to build databases for partial least square (PLS) regression analysis. PLS models will be used for additional discovery of new AChE-inhibitory peptides. Using the Wistar rat model, peptides with strongest potency against AChE will be evaluated for ability to cross the BBB and reduce brain activity of AChE. The proposed work is significant because the results will provide fundamental scientific information on the amino acid structural requirements for AChE-inhibitory peptides. Such structural information will enable development of peptide-based nutritional tools that can normalize physiological disorders associated with the nervous system. The proposed work for this 5-yr cycle will train 3 postdoctoral fellows, 2 PhD students, 3 MSc students and 5 undergraduate summer research students.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Spectrofluorimeter for protein and peptide research
-
批准号:RTI-2023-00523
-
项目类别:Research Tools and Instruments
-
资助金额:$3.16万
-
财政年份:2022
-
负责人:Aluko, Rotimi
-
依托单位:
Quantitative structure-activity relationship studies of acteylcholinesterase-inhibitory peptides
-
批准号:RGPIN-2018-06019
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$3.42万
-
财政年份:2022
-
负责人:Aluko, Rotimi
-
依托单位:
Bioactive peptides
-
批准号:CRC-2020-00290
-
项目类别:Canada Research Chairs
-
资助金额:$14.57万
-
财政年份:2022
-
负责人:Aluko, Rotimi
-
依托单位:
Bioactive Peptides
-
批准号:CRC-2020-00290
-
项目类别:Canada Research Chairs
-
资助金额:$14.57万
-
财政年份:2021
-
负责人:Aluko, Rotimi
-
依托单位:
Quantitative structure-activity relationship studies of acteylcholinesterase-inhibitory peptides
-
批准号:RGPIN-2018-06019
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$3.42万
-
财政年份:2021
-
负责人:Aluko, Rotimi
-
依托单位:
FPLC System for Bioactive Peptides Research
-
批准号:RTI-2021-00371
-
项目类别:Research Tools and Instruments
-
资助金额:$8.15万
-
财政年份:2020
-
负责人:Aluko, Rotimi
-
依托单位:
Quantitative structure-activity relationship studies of acteylcholinesterase-inhibitory peptides
-
批准号:RGPIN-2018-06019
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$3.42万
-
财政年份:2020
-
负责人:Aluko, Rotimi
-
依托单位:
Quantitative structure-activity relationship studies of acteylcholinesterase-inhibitory peptides
-
批准号:RGPIN-2018-06019
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$3.42万
-
财政年份:2018
-
负责人:Aluko, Rotimi
-
依托单位:
Purchase of a preparative HPLC system for bioactive peptides research
-
批准号:RTI-2018-00531
-
项目类别:Research Tools and Instruments
-
资助金额:$6.86万
-
财政年份:2017
-
负责人:Aluko, Rotimi
-
依托单位:
Structure-function properties of food protein-derived calmodulin-binding peptides: in vivo studies
-
批准号:249890-2013
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$4.15万
-
财政年份:2017
-
负责人:Aluko, Rotimi
-
依托单位:
Optimization of gelatin production from acid soluble collagen extracted from egg shell membrane
-
批准号:520366-2017
-
项目类别:Engage Plus Grants Program
-
资助金额:$0.35万
-
财政年份:2017
-
负责人:Aluko, Rotimi
-
依托单位:
Development of a production method to isolate acid-soluble collagen from eggshell membranes
-
批准号:507361-2016
-
项目类别:Engage Grants Program
-
资助金额:$1.82万
-
财政年份:2016
-
负责人:Aluko, Rotimi
-
依托单位:
Structure-function properties of food protein-derived calmodulin-binding peptides: in vivo studies
-
批准号:249890-2013
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$4.15万
-
财政年份:2016
-
负责人:Aluko, Rotimi
-
依托单位:
Optimization of industrially defatted flaxseed meal fibre digestion to enhance production of commercial-grade protein isolates
-
批准号:485675-2015
-
项目类别:Engage Grants Program
-
资助金额:$1.82万
-
财政年份:2015
-
负责人:Aluko, Rotimi
-
依托单位:
Structure-function properties of food protein-derived calmodulin-binding peptides: in vivo studies
-
批准号:249890-2013
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$4.15万
-
财政年份:2015
-
负责人:Aluko, Rotimi
-
依托单位:
Structure-function properties of food protein-derived calmodulin-binding peptides: in vivo studies
-
批准号:249890-2013
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$4.15万
-
财政年份:2014
-
负责人:Aluko, Rotimi
-
依托单位:
Structure-function properties of food protein-derived calmodulin-binding peptides: in vivo studies
-
批准号:249890-2013
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$4.15万
-
财政年份:2013
-
负责人:Aluko, Rotimi
-
依托单位:
Quantitative structure-activity relationship study of food protein-derived calmodulin-binding peptides
-
批准号:249890-2007
-
项目类别:Discovery Grants Program - Individual
-
资助金额:$2.48万
-
财政年份:2012
-
负责人:Aluko, Rotimi
-
依托单位:
Optimization of Hibiscus flower extraction for high yield and antioxidant potency of the polyphenolic compounds
-
批准号:435457-2012
-
项目类别:Engage Grants Program
-
资助金额:$1.82万
-
财政年份:2012
-
负责人:Aluko, Rotimi
-
依托单位:
Bioactive pea protein hydrolysate: pilot plant scale-up and beverage formulation (Phase 1)
-
批准号:428620-2012
-
项目类别:Idea to Innovation
-
资助金额:$8.6万
-
财政年份:2012
-
负责人:Aluko, Rotimi
-
依托单位:
国内基金
海外基金
登录
查看更多内容
Rh-N4位点催化醇类氧化反应的微观机制与构效关系研究
-
批准号:22302208
-
项目类别:青年科学基金项目
-
资助金额:30.00万元
-
批准年份:2023
-
负责人:王翔
-
依托单位:
体内亚核小体图谱的绘制及其调控机制研究
-
批准号:32000423
-
项目类别:青年科学基金项目
-
资助金额:24.0万元
-
批准年份:2020
-
负责人:温增麒
-
依托单位:
水稻H3K27me3标记基因的三维基因组结构解析及其调控抽穗期的机理研究
-
批准号:32070612
-
项目类别:面上项目
-
资助金额:58.0万元
-
批准年份:2020
-
负责人:李兴旺
-
依托单位:
稻瘟病菌中蛋白激酶MoCK2参与附着胞极性生长影响致病性的初步探索
-
批准号:32060597
-
项目类别:地区科学基金项目
-
资助金额:35.0万元
-
批准年份:2020
-
负责人:张连虎
-
依托单位:
CTCF/cohesin介导的染色质高级结构调控DNA双链断裂修复的分子机制研究
-
批准号:32000425
-
项目类别:青年科学基金项目
-
资助金额:24.0万元
-
批准年份:2020
-
负责人:寿佳
-
依托单位:
一个全基因组尺度示踪染色质环重新生成的方法
-
批准号:32070611
-
项目类别:面上项目
-
资助金额:58.0万元
-
批准年份:2020
-
负责人:徐晨欢
-
依托单位:
多层次纳米叠层块体复合材料的仿生设计、制备及宽温域增韧研究
-
批准号:51973054
-
项目类别:面上项目
-
资助金额:60.0万元
-
批准年份:2019
-
负责人:王建锋
-
依托单位:
异染色质修饰通过调控三维基因组区室化影响机体应激反应的分子机制
-
批准号:31970585
-
项目类别:面上项目
-
资助金额:58.0万元
-
批准年份:2019
-
负责人:卞迁
-
依托单位:
骨髓间充质干细胞成骨成脂分化过程中染色质三维构象改变与转录调控分子机制研究
-
批准号:31960136
-
项目类别:地区科学基金项目
-
资助金额:40.0万元
-
批准年份:2019
-
负责人:滕兆伟
-
依托单位:
染色质三维结构等位效应的亲代传递研究
-
批准号:31970586
-
项目类别:面上项目
-
资助金额:58.0万元
-
批准年份:2019
-
负责人:彭城
-
依托单位: