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RSC Advances · 2018 ·Vol. 8 ·期 27 ·14967-14974 · IF 2.936

Hypoglycemic effect and mechanism of isoquercitrin as an inhibitor of dipeptidyl peptidase-4 in type 2 diabetic mice

Lei Zhang,Shi-Tao Zhang,Yan-Chun Yin,Shu Xing,Wan-Nan Li,Xue-Qi Fu

Glucagon-like peptide (GLP)-1 is a potent glucose-dependent insulinotropic gut hormone released from intestinal L cells. The aim of this study was to investigate isoquercitrin as an inhibitor of dipeptidyl peptidase IV (DPP-IV) and determine whether it affects GLP-1 release in normal mice and NCI-H716 cells. In vitro, we used chromogenic substrate method detection methods to measure DPP-IV. We found that isoquercitrin was a competitive inhibitor, with IC50 and Ki values of 96.8 and 236 μM, respectively. Isoquercitrin and sitagliptin also stimulated GLP-1 release in NCI-H716 cells. In vivo, a type 2 diabetic mouse model was established, and oral treatment with different concentration of isoquercitrin and sitagliptin for 8 weeks significantly decreased the fasting blood glucose level. The weight and the levels of serum GLP-1 and insulin of the mice in the isoquercitrin group were higher than those in the model group (P < 0.001). An oral glucose tolerance test showed that the isoquercitrin significantly inhibited postprandial blood glucose changes in a dose-dependent manner. These findings demonstrated the hypoglycemic effects of isoquercitrin and indicated that isoquercitrin improved insulin sensitivity by targeting DPP-IV.

CAS / MDL: 482-35-9 486460-32-6
研究领域: 药理学 · 内分泌学 · 分子生物学
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INDUSTRIAL CROPS AND PRODUCTS · 2024 · IF 5.6

Activity and mechanism of α-glucosidase inhibitory peptides released from Osmanthus fragrans seeds protein during the in vitro digestion

Jun-Hui Du,Dong-Mei Yang,Tong-Tong Guan,Jie Wang,Yi-Long Ma,Zhao-Jun Wei

Osmanthus fragrans seeds (OFSs) abundant in protein are valuable resources of bioactive peptides. To elucidate the potential hypoglycemic peptides released during the digestion, OFSs protein was extracted and digested in vitro . The effects of the digestion step and molecular weight on the α-glucosidase inhibitory ability of the digested protein were evaluated, and the mechanism and structure of the main effective peptides in the digesta were studied. The results indicated that the digesta after the small intestine digestion displayed higher inhibition (58.5 %), from which the fraction below 3 kDa was more effective (67.34 %). Among the seven sub-fractions (F1∼F7) below 3 kDa, F1 obtained the highest α-glucosidase inhibitory ability (60.69 %). Three peptides (ERFQ, VHHK, and EKFMKE) were identified from F1, and their efficacy was verified by corresponding synthetic peptides, showing the α-glucosidase inhibitory rates of 79.1 % ± 2.24 %, 65.67 % ± 1.97 % and 61.94 % ± 1.97 %, respectively. According to the molecular docking, these peptides inhibited the α-glucosidase by forming secondary forces (e.g. hydrophobic interaction) with the key amino acids (e.g. D327, D443, Y299, and F575) of the enzyme, with docking scores ranging from −151.038 to −171.907. This study demonstrated OFSs could release α-glucosidase inhibitory peptides during digestion and may serve as functional ingredients to control diabetes.

研究领域: 食品科学 · 生物化学 · 药理学
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Journal of Materials Chemistry B · 2024 · IF 6.1

Sensitive detection of dipeptidyl peptidase based on DNA–peptide conjugates and double signal amplification of CHA and DNAzymes

Yan Chen,Miao He,Feifan Yin,Wenting Cheng,Zhongyun Wang,Yang Xiang

Dipeptidyl peptidase IV (DPPIV) is an enzyme belonging to the type II transmembrane serine protease family that has gained wide interest in the fields of hematology, immunology, and cancer biology. Moreover, DPPIV has emerged as a promising target for therapeutic intervention in type II diabetes. Due to its biological limitations, traditional strategies cannot meet the requirements of low abundance DPPIV analysis in complex environments. In this work, combining the high programmability of DNA and the chemical diversity of peptides, we designed DNA–peptide conjugates that can be specifically recognized, polypeptides as specific substrates for target DPPIV and DNA probes as primers for catalytic hairpin assembly (CHA), recycling a large amount of DNAzymes by triggering CHA amplification. The DNAzyme substrate modified with the FAM fluorescent group was immobilized on the surface of gold nanoparticles by S–Au chemical bonds to form a signal output probe. The DNAzymes enzyme cleaved the substrate of the signal outputs probe, yielding a double-amplified fluorescence signal. This method has a detection limit as low as 0.18 mU mL−1 and a linear range of 0–5 mU mL−1 in serum samples, showing high stability and good potential for practical applications.

研究领域: 生物化学 · 分子生物学 · 分析化学 · 糖尿病研究 · 癌症生物学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2022 · IF 9.965

Cofactors-like peptide self-assembly exhibiting the enhanced catalytic activity in the peptide-metal nanocatalysts

Tongtong Sun,Yonghai Feng,Jiali Peng,Yun Hao,Liwei Zhang,Lei Liu

The peptide self-assembly would be expected to be as the assistance of metallic nanocatalysts to promote the catalytic reaction, attracting limited attention, but being highly anticipated. Herein, we proposed and verified an alternative strategy for enhancing the catalytic activity of the 4-nitrophenol reduction as a model reaction, by optimizing and constructing “cofactors” inspired amyloid peptide self-assembly applied in the peptide-metal nanocatalysts as the template due to the potential superiority of substrate binding. Amyloid peptide self-assembled membrane exhibited better enhanced catalytic activity, compared to peptide nanofibers as the template in the peptide-gold nanocatalysts. The optimized amyloid peptide was designated by molecular dynamic simulation to display the relative strongest interaction with specific substrate and the relative good template effect on the enhanced catalytic activity was also proved accordingly. This work may shed light on the future design and construction of novel enzyme mimics with dramatic enhanced catalytic activity by peptide assembly-metal nanocatalysts.

研究领域: 纳米技术 · 生物化学 · 催化
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JOURNAL OF FOOD SCIENCE · 2023 ·Vol. 88 ·期 8 ·3577-3593 · IF 3.9

Preparation, identification, and inhibitory mechanism of dipeptidyl peptidase IV inhibitory peptides from goat milk whey protein

Xiaojing Du,Chengyu Jiang,Shan Wang,Huijuan Jing,Ling Mo,Chaoyang Ma,Hongxin Wang

This study explores potential hypoglycemic mechanisms by preparing and identifying novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from goat milk (GM) whey protein. Papain was used to hydrolyze the GM whey protein. After purification by ultrafiltration, the Sephadex column, and preparative RP-HPLC, the peptide inhibited DPP-IV, α-glucosidase, and α-amylase with IC50 of 0.34, 0.37, and 0.72 mg/mL, respectively. To further explore the inhibitory mechanism of peptides on DPP-IV, SPPEFLR, LDADGSY, YPVEPFT, and FNPTY were identified and synthesized for the first time, with IC50 values of 56.22, 52.16, 175.7, and 62.32 µM, respectively. Molecular docking and dynamics results show that SPPEFLR, LDADGSY, and FNPTY bind more tightly to the active pocket of DPP-IV, which was consistent with the in vitro activity. Furthermore, the first three N-terminals of SPPEFLR and FNPTY peptides exhibit proline characteristics and competitively inhibit DPP-IV. Notably, the first N-terminal leucine of LDADGSY may play a key role in inhibiting DPP-IV.

CAS / MDL: 75-05-8 76-05-1 643-79-8
研究领域: 食品科学 · 生物化学 · 药理学
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Food Chemistry-X · 2024 · IF 6.5

Evaluation of UHT milk spoilage caused by proteases from psychrophilic bacteria based on peptidomics

Jinyu Xu,Xiaodan Wang,Xiaoxuan Zhao,Hongyu Cao,Yunna Wang,Ning Xie,Xu Li,Xiaoyang Pang,Jiaping Lv,Shuwen Zhang

The quality issues of ultra-high-temperature (UHT) milk, such as protein hydrolysis and aging gels throughout shelf life, are caused by proteases from psychrophilic bacteria. However, existing enzyme activity detection techniques have low sensitivity and cannot accomplish the detection of product deterioration caused by low enzyme activity. In this study, an attempt was made to analyze the relationship between enzymatically cleaved peptides and product quality using peptidomics techniques. The impact of psychrophilic bacteria proteases on the quality of UHT milk was investigated based on peptidomics by exogenously adding proteases. The results indicated that the protease activity and protein hydrolysis increased significantly in UHT milk over the storage period. Through peptidomic analysis, 2479 peptides were identified, in which 32 proteins linked to the identified peptides. 17 potential marker peptides, including αS 1 -casein 143–156 , β -lactoglobulin 99–108 , and β -casein 39–66 , were screened. The correlation of all identified peptides with protease activity and protein hydrolysis was explored by the weighted gene co-expression network analysis (WGCNA) method. The peptidomics technology helps to study the release or degradation of peptides in UHT milk during storage, which can be applied to monitor the shelf life of UHT milk and predict spoilage.

CAS / MDL: 60-24-2 643-79-8
研究领域: 食品科学 · 微生物学 · 蛋白质组学
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Advanced Fiber Materials · 2022 ·Vol. 4 ·期 3 ·448-456 · IF 12.958

Effect of Microwave Irradiation on Dipeptides and Proteins Derived from Silk During Solvation

Li Na,Ma Ying,Chen Niuniu,Tang Xiaoyu,Lv Shanshan

Silkworm silk and spider silk have been attracting numerous interests. Rapid solvation of silkworm silk protein and spider silk protein without hydrolysis of peptide bonds is highly desirable. Microwave irradiation has been proposed for facile extraction of water-soluble silk protein by various liquid media. However, microwave exposure can cause hydrolysis of peptide bonds, leading to irreversible degradation of silk protein. In this study, a series of representative dipeptides and a rationally designed recombinant protein derived from silk protein is employed to investigate the effect of microwave on the stability of the peptide bonds during a long time dissolution process, i.e., heating at 60 ℃ in a CaCl 2 :CH 3 CH 2 OH:H 2 O (1:2:8) solution. Results demonstrate that microwave irradiation imposes a minor damage and a negligible cleavage of the peptide bonds, compared with the conventional heating method. The microwave irradiation treatment suggested in this is suitable for dissolution of silk protein. It is anticipated that this approach can be developed to a commercial level commercially.  Graphical abstract

研究领域: 生物化学 · 材料科学
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Nanoscale · 2021 ·Vol. 13 ·期 9 ·5094-5102 · IF 7.79

Molecular self-assembly of a tyroservatide-derived octapeptide and hydroxycamptothecin for enhanced therapeutic efficacy

Jing Liu,Can Wu,Guoru Dai,Feng Feng,Yuquan Chi,Keming Xu,Wenying Zhong

Tyroservatide (YSV) belongs to a class of bioactive peptides that have drawn considerable attention in the field of drug discovery, yet it displays limited potency and often requires a millimolar concentration to execute its cellular functions. To enhance the potency of the drug through a self-assembling strategy, we designed and synthesized a series of octapeptides through conjugation of YSV with a pentapeptide sequence bearing alternating hydrophobic and hydrophilic amino acids to promote their self-assembling capabilities. Initial screening for hydrogelation gave a novel octapeptide (denoted as 1-YSV hereafter) that was capable of self-assembling under physiological conditions to afford supramolecular nanofibers with enhanced anti-cancer efficacy compared to YSV itself. Interestingly, 1-YSV formed a robust co-assembly with the anticancer drug hydroxycamptothecin (HCPT) to afford 1-YSV/HCPT hydrogel, which not only greatly improved the viscoelastic properties of hydrogels, but also stabilized HCPT in the hydrogel matrix and avoided the agglomeration of drug molecules. Compared to HCPT solution, the hydrogel formulation of 1-YSV/HCPT demonstrated better efficacy against the proliferation of non-small cell lung cancer A549 cells both in vitro and in vivo. Finally, thanks to the pure amino acid-based composition, the 1-YSV/HCPT formulation exhibited excellent biocompatibility, giving a low hemolytic rate to red blood cells, with mild local tissue reactions and negligible systematic toxicities in mice.

研究领域: 药学 · 生物材料学 · 肿瘤学
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LWT-FOOD SCIENCE AND TECHNOLOGY · 2024 · IF 6

Investigation of the antioxidative potential of Meretrix meretrix L. derived peptides from simulated gastrointestinal digestion: In vitro and in silico insights

Chao Du,Zhenzhen Hui,Na Li,Kaiyue Liu,Yong Wang,Ping Wang,Shuyang Sun

This investigation sought to identify antioxidative peptides derived from Meretrix meretrix L. (MML) throughout simulated gastrointestinal digestion (SGD) via in vitro and in silico strategies. The study demonstrated that hydrolysates from MML captured at various SGD phases showcased robust antioxidative activity. These hydrolysates also displayed a protective role against hydrogen peroxide-induced stress in Raw 264.7 cells. Notably, hydrolysates sourced from the intestinal phase of digestion (MMLHs-I) markedly inhibited the reduction of cell viability, limited the generation of reactive oxygen species under oxidative stress conditions, and promoted the activity of key antioxidant enzymes including superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, thus amplifying the cells' antioxidative defense system. Through nLC-MS/MS analysis, 105 peptides tracing back to 18 parent proteins were pinpointed in MMLHs-I, with 18 of these peptides previously reported in the BIOPEP-UWM database. Subsequent in silico analysis, alongside empirical antioxidant activity assays, pinpointed the peptide WLV as an exceptional antioxidative agent, demonstrating an IC 50 of 0.125 mg/mL in the ABTS assay and an impressive 15.18 μmol Trolox/mg in the ORAC assay. The outcomes highlight MML's promise as a novel source of antioxidative peptides, positioning peptide WLV as a potentially valuable addition to functional foods designed to combat oxidative stress.

研究领域: 食品科学 · 生物化学
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

In Situ MXene-Controlled Synthesis of Polycrystalline TiO2 for Highly Efficient Enrichment of Phosphopeptides

Feifei Xu,Danyi Shang,Congcong Zhu,Guangzhu Du,Jingchen Shi,Xuefang Dong,Xiuling Li,Xinmiao Liang

Phosphopeptide enrichment methods based on commercial TiO2 suffer from difficulties in regulating intermolecular interactions, resulting in low coverage rate and the loss of information on multiphosphorylation sites, thereby limiting comprehensive phosphoproteomic analysis. In this work, MXene Ti3C2Tx was incorporated into the design of enrichment materials, with its surface structure functionalized and regulated to address the low elution efficiency of TiO2 for multiphosphorylated peptides. Upon oxidation treatment, the Ti3C2Tx material formed numerous uniformly distributed TiO2 nanoparticles on the surface of Ti3C2Tx-O, providing abundant affinity sites (Ti–O) for selective phosphopeptide enrichment. The polycrystalline structure and rich oxygen vacancies of the material effectively regulated its binding affinity with phosphate groups, achieving simultaneous high-efficiency enrichment of both monophosphorylated and multiphosphorylated peptides. Its performance was significantly superior to that of commercial TiO2 and IMAC materials. This study presents great promise for the practical application of comprehensive phosphoproteomic analysis in the future and broadens the application of MXene in the biological field.

研究领域: 分析化学 · 生物化学 · 材料科学
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RSC Advances · 2018 ·Vol. 8 ·期 54 ·30887-30893 · IF 2.936

Novel oligopeptide nanoprobe for targeted cancer cell imaging

Wen-Qiang Ding,Si-Yong Qin,Yin-Jia Cheng,Yi-Han Ma,Ai-Qing Zhang

Here we designed and constructed a tryptophan-phenylalanine-phenylalanine-tryptophan (WFFW) tetrapeptide, which generated photostable and tunable fluorescence emission signals from 340 nm to 500 nm. The WFFW tetrapeptide could self-assemble into a spherical nanostructure with enhanced fluorescence intensity. Driven by π–π stacking and hydrogen bond interaction, WFFW co-assembled with arginine-glycine-aspartic acid (RGD) modified WFFW to form a cancer-targeted fluorescent nanoprobe, which could selectively image the cancer cells.

研究领域: 生物化学 · 医学影像 · 纳米医学
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CHEMISTRY OF MATERIALS · 2017 · IF 9.466

One-Pot Synthesis of Polysaccharide–Diphenylalanine Ensemble with Gold Nanoparticles and Dye for Highly Efficient Detection of Glutathione

Qiuju Li,Anan Sun,Yinsong Si,Min Chen,Limin Wu

Glutathione (GSH) plays a crucial role in various physiological processes. Therefore, efficient detection of GSH is of great importance. In this study, we present a new and highly efficient ratiometric fluorescent biosensor through one-pot synthesis of coupling the self-assembly of polysaccharide (alginate dialdehyde, ADA)-dipeptide (diphenylalanine, FF) and in situ reduction of gold nanoparticles (Au NPs) simultaneously encapsulating a dye (5-aminofluorescein, FI-NH2) inside to form ADA-Au-FF-dye nanospheres. Because the fluorescence of the dye can be quenched by Au NPs and linearly recovered following the introduction of different GSH concentrations owing to nanometal surface energy transfer on and off, this new ADA-Au-FF-dye hybrid nanosphere-based sensor allows label-free and ratiometric detection of intracellular GSH and other biothiols in a wide linear range, which is of great significance for cancer diagnostics and therapy.

研究领域: 生物化学 · 纳米医学 · 癌症诊断
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