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BIOMATERIALS · 2014 · IF 8.312

Anti-tumor efficacy of c(RGDfK)-decorated polypeptide-based micelles co-loaded with docetaxel and cisplatin

Wantong Song,Zhaohui Tang,Dawei Zhang,Ying Zhang,Haiyang Yu,Mingqiang Li,Shixian Lv,Hai Sun,Mingxiao Deng,Xuesi Chen

There are two important obstacles for the currently applied anti-cancer drug delivery systems. One is the conflict between long-circulation and cellular uptake while the other one is the achievement of ideal anti-cancer efficacy. To solve these problems, we designed a polypeptide-based micelle system that combined the advantages of receptor mediated endocytosis and multi-drug delivery. Firstly, an amphiphilic PLG- g -Ve/PEG graft copolymer was prepared by grafting α-tocopherol (Ve) and polyethylene glycol (PEG) to poly( l -glutamic acid) (PLG). Then docetaxel (DTX) and cisplatin (CDDP) were co-loaded into the PLG- g -Ve/PEG micelles via hydrophobic and chelation effect. After that, the surface of the dual-drug-loaded micelles was decorated with an α v β 3 integrin targeting peptide c(RGDfK). The targeted dual-drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In vivo tests demonstrated that remarkable long circulation, anti-tumor and anti-metastasis efficacy could be achieved using this drug delivery system. This work revealed a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy.

研究领域: 药学 · 肿瘤学 · 生物材料
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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 39 ·7963-7973 · IF 4.543

Replacement of quaternary ammonium headgroups by tri-ornithine in cationic lipids for the improvement of gene delivery in vitro and in vivo

Y. N. Zhao,Y. Z. Piao,C. M. Zhang,Y. M. Jiang,A. Liu,S. H. Cui,D. F. Zhi,Y. H. Zhen,S. B. Zhang

Headgroups in cationic lipids play very important roles in determining transfection efficiency and toxicity in gene delivery. To better understand the influence of headgroups on gene delivery, a tri-peptide-based lipid was synthesized, wherein the usual quaternary ammonium was replaced by a tri-peptide. Though both the tri-peptide-based lipid (DAO3) and the quaternary ammonium-based lipid (DDCTMA) successfully mediated gene transfection, DAO3 was superior to DDCTMA in both in vitro and in vivo studies. Following their preparation into liposomes, the particle size, zeta potential, and DNA-binding capacity of the liposomes and lipoplexes were characterized to evaluate the efficiency of DAO3 compared to DDCTMA with regard to gene interactions. The expression of luciferase from pDNA mediated by DAO3 was 2-fold greater than than that with DDCTMA in Hep-2 cells, and DAO3/siRNA lipoplexes could silence about 60% luciferase in A549 cancer cells expressing firefly luciferase. DAO3/Luc-siRNA treatment exhibited 3-fold the efficiency of DDCTMA/Luc-siRNA in terms of in vivo luciferase RNAi with the bare density ratio of 0.54 at 48 h. Furthermore, DAO3 could mediate IGF-1R siRNA to inhibit tumor growth through silencing the expression of the IGF-1R protein, whereas DDCTMA showed nearly no effects. Most importantly, DAO3 had no obvious toxicity in vitro and in vivo, due to the biocompatibility of the peptide headgroups. In conclusion, these results demonstrated that the replacement of the quaternary ammonium headgroup by tri-ornithine may increase transfection efficiency and decrease toxicity.

研究领域: 分子生物学 · 基因治疗 · 药物递送
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ANALYTICAL BIOCHEMISTRY · 2021 · IF 3.365

Peptide-based system for sensing Pb2+ and molecular logic computing

Jiao Yang Lu,Fu Rui Zhang,Wen Zi Zou,Wei Tao Huang,Zhen Guo

Peptides with recognition, assembly, various activities exhibit strong power and application prospects in sensing, material science, biomedicine . However, peptide-based sensing and expanding application is still at an early stage. Herein, a peptide-based sensing and logic system was developed for highly sensitive and selective detection of Pb 2+ and implementation of logic operations. Our Pb 2+ assay method was ultra-rapid (less than 1 min), direct, simple with detection limit of 0.75 nM. Flexibility and scalability of peptide-based solution system facilitated the execution of sensing and logic operations from simple to complex. This research will not only inspire discovery and comprehensive applications (such as sensing and assembly) of more functional peptides, but also provide more opportunities for development and design of peptide-based systems and molecular information technologies.

研究领域: 生物化学 · 分析化学 · 分子生物学
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ChemElectroChem · 2017 ·Vol. 4 ·期 3 ·472-475 · IF 4.136

A Peptide-Based Electrochemical Biosensor for Facile Measurement of Whole-Blood Heparin

Fanyu Meng,Weiguo Liang,Haixuan Sun,Ligang Wu,Xiao Gong,Peng Miao

Graphical Peptide–heparin composites : A simple electrochemical approach for the determination of heparin level in human whole-blood is developed based on specific peptide recognition (see picture). The first peptide-based electrochemical biosensor for the measurement of the anti-coagulant heparin using electrochemical impedance spectroscopy is reported. The peptide immobilized on the electrode interface specially captures heparin with high affinity. The composites formed on the electrode can thus effectively repel electrochemical species, leading to an increase in interfacial charge transfer resistance. After analyzing the electrochemical signals, a linear detection range from 0.05 to 10.0 μg/mL is obtained. The detection limit is calculated to be 0.01 μg/mL, which is extremely low with such a simple sensing mechanism. Moreover, the proposed method has potential application for sensitive and separation-free detection of heparin in whole-blood samples.

研究领域: 生物化学 · 医学检测 · 电化学
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Nanoscale · 2019 ·Vol. 11 ·期 9 ·3864-3876 · IF 6.97

Probing a dipeptide-based supramolecular assembly as an efficient camptothecin delivering carrier for cancer therapy: computational simulations and experimental validations

Mengchi Sun,Xiangyu Zhang,Zisen Gao,Tian Liu,Cong Luo,Yongshan Zhao,Yun Liu,Zhonggui He,Jian Wang,Jin Sun

Short peptide-based supramolecular assemblies have drawn much attention in the field of drug delivery. However, the progress still remains limited owing to the inefficient drug loading capacity of conventional short peptide-based materials. In this study, based on coordinated intramolecular π–π stacking, we customize a dipeptide-based rhein derivative (rhein–diphenylalanine peptide, RDP), which could spontaneously form spherical nanoassemblies for drug delivery. A structure-based virtual screening of a library of small molecules is conducted to identify the suitable compounds which could be effectively delivered by this nanocarrier. Sorted by binding energy results, fifteen superior and five inferior molecules are found. Subsequently, the co-assembly capacity of high-affinity molecules (camptothecin, CPT) and low-affinity molecules (norcantharidin, NCTD) with the dipeptide-based carrier is predicted via dissipative particle dynamics (DPD) simulation. Consistent with computational results, the in vitro experimental results show that CPT-encapsulated nanoassemblies have significant advantages in the particle size distribution and recrystallization-inhibitory effect compared with NCTD. Furthermore, in vivo experiments were conducted to determine whether CPT is precisely delivered to tumor sites by using the dipeptide-based nanoassemblies. The CPT-loaded nanoassemblies show better effects in terms of drug biodistribution and in vivo anti-tumor efficacy compared to free CPT. The cooperative computational and experimental strategies (in vitro and in vivo) used in this work lay a good foundation to systematically understand short peptide-based assemblies for precise drug delivery.

研究领域: 药物递送 · 生物医学工程 · 肿瘤学
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FOOD CHEMISTRY · 2025 · IF 9.8

Identification and characterization of two novel dipeptidyl peptidase-IV inhibitory peptides from the simulated gastrointestinal digestion of Tartary buckwheat proteins

Weijing Wu,Ju Qiu,Libo Wang,Qianglai Tan,Ziyuan Zhuang,Yanling Wang,Lanlan Wu

This study analyzed dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides from Tartary buckwheat ( Fagopyrum tataricum ) protein hydrolysates, known for managing chronic diseases. Simulated gastrointestinal digestion enhanced the inhibitory activity of DPP-IV. Using anion-exchange resin DEAE-52, reverse high-performance liquid chromatography, and LC-MS/MS, eight novel peptides were identified. Among them, the peptides LAGQS (LA5) and LREIDDADK (LR9) exhibited the strongest inhibition in both competitive and noncompetitive modes. Molecular docking revealed electrostatic, hydrogen bond, and hydrophobic interactions for both peptides, with LR9 also engaging in π-cation interactions. Based on the Caco-2 model, the in situ DPP-IV inhibitory effect of LR9 was superior to that of LA5, likely because of LR9's greater stability during hydrolysis. Moreover, LA5 could not be transported through the Caco-2 monolayer, and LR9 demonstrated moderate transportability. These findings highlight Tartary buckwheat protein's potential for application in high-value plant-based products, including functional foods and pharmaceuticals targeting blood glucose regulation using DPP-IV inhibitory peptides.

CAS / MDL: 8049-47-6
研究领域: 食品科学 · 生物化学
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CHINESE JOURNAL OF POLYMER SCIENCE · 2021 ·Vol. 39 ·期 11 ·1412-1420 · IF 3.603

Biodegradable Polypeptide-based Vesicles with Intrinsic Blue Fluorescence for Antibacterial Visualization

Yang Yu-Ying,Chen Ling-Shan,Sun Min,Wang Cong-Yu,Fan Zhen,Du Jian-Zhong

Fluorescence imaging has been an indispensable tool to provide dynamic information about the localization and quantity of organisms. Meanwhile, due to the intrinsic hollow structure and modularized biofunctionalities, polymer vesicles have been widely applied in biomedical field. However, most polymer vesicles are embedded with organic fluorophores for fluorescence imaging, which have certain drawbacks such as leakage and possible cytotoxicity. Here, we present a biodegradable polypeptide-based vesicle with intrinsic blue fluorescence without introducing any fluorophore for real-time visualization of antibacterial process. Through modular design to integrate multiple functional fragments, poly( ε -caprolactone)-block-poly(tryptophan)-block-poly(lysine- stat -phenylalanine) [PCL 25 - b -PTrp 2 - b -P(Lys 13 - stat -Phe 4 )] was synthesized, where PCL chains form the hydrophobic membrane, P(Lys- stat -Phe) and PTrp provide intrinsic fluorescence and broad-spectrum antibacterial activity. It is noteworthy that the fluorescence emission was shifted from invisible ultraviolet range of amino acids to visible range (emission maximum at 436 nm), which makes it possible to visualize the antibacterial process. In addition, through utilizing the intrinsic fluorescence of vesicles, confocal fluorescent imaging of vesicles with bacteria validated the specific adhesion of vesicle towards bacteria, and the bacterial death through membrane disruption. Overall, we provided a novel approach to developing biodegradable fluorescent polypeptide-based vesicles for real-time visualization of antibacterial process.

研究领域: 生物材料学 · 医学影像学 · 生物化学
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TALANTA · 2023 · IF 6.1

Peptide-antifouling interface for monitoring β-amyloid based on electrochemiluminescence resonance energy transfer

Yinan Li,Zixuan Chen,Wen Li,Fei Zhang,Xiaoyan Yang,Caifeng Ding

In this study, a novel antifouling electrochemiluminescence (ECL) analytical platform has been developed for the highly sensitive quantification of β -amyloid (A β ) peptides based on the ECL resonance energy transfer (ECL-RET) mechanism. Specifically, glassy carbon electrodes (GCE) were initially coated with graphite-phase carbon nitride (g-C 3 N 4 ) nanosheets , followed by the electropolymerization of polyaniline (PANI) onto the electrode surface. Subsequently, a promising peptide motif candidate (COOH-CPPPPDKDKDKDKKLVFF) was immobilized onto the PANI-modified electrode, functioning as a critical component for both antifouling and specific recognition of full-length A β peptides. Furthermore, this peptide motif demonstrated inhibitory effects on A β aggregation and dissociation. Upon immobilization of the peptide motif, A β aptamer-CdS QDs were bound to the electrode surface through peptide-specific interactions with Aβ, thereby facilitating the highly sensitive ECL detection of A β . Under the optimal conditions, the proposed biosensor exhibited an A β detection range from 0.1 pM to 100 nM with a detection limit of 16.1 fM. As such, this innovative platform offers a straightforward approach to antifouling, quantification, and monitoring of A β concentrations in the blood samples.

研究领域: 生物医学工程 · 神经科学 · 分析化学
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Journal of Materials Chemistry B · 2023 ·Vol. 11 ·期 26 ·6141-6146 · IF 7

Improving the catalytic ability of a peptide-based artificial glycosidase through a tyrosine strategy

Lijun Yang,Yi Tian,Yutong Wang,Wei Qi,Mengfan Wang

Recently, peptide-based artificial enzymes have attracted growing interest due to the similar composition of peptide assemblies to natural enzymes. However, low catalytic activity and stability are still the main challenges for these enzyme-like catalysts. In this study, a tyrosine strategy was developed to construct a peptide-based artificial glycosidase through engaging the Tyr residue into the peptide sequence. We found that the appropriate substitution of Tyr produced an enhanced catalytic ability, because the proximal Tyr residue around catalytic sites acts as a nucleophile, playing an important role in the substrate orientation and proton transfer. Moreover, inspired by the biological function of dityrosine bonds in structural proteins, a photo-crosslinking reaction between the phenolic side chains of Tyr was also employed to form intermolecular covalent bonds in peptide assemblies, which further improved the activity and stability of the artificial glycosidase. This work provides a simple avenue for the designing and construction of efficient glycosidase-like catalysts based on a peptide-based material platform.

CAS / MDL: 3150-24-1 100-02-7
研究领域: 生物化学 · 酶工程 · 合成生物学
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Journal of Materials Chemistry B · 2019 ·Vol. 7 ·期 24 ·3804-3810 · IF 5.047

Constructing peptide-based artificial hydrolases with customized selectivity

Mingjie Zhu,Mengfan Wang,Wei Qi,Rongxin Su,Zhimin He

Peptide-based materials are promising building blocks for the fabrication of artificial enzymes due to their proteic nature and tailorable structure. However, it is still a big challenge to create artificial enzymes with designable selectivity. In this study, the molecular imprinting strategy was combined with the self-assembly of Fmoc-FFH to create an artificial hydrolase with specific selectivity. By using p-NPA as the imprinting template, we found that the imprinted polymer that was coated on the surface of the catalytic peptide nanofibers provided a specific binding site to p-NPA, hence enhancing the catalytic efficiency of the artificial hydrolase. Furthermore, we confirmed that the substrate selectivity of this artificial enzyme can be customized by changing the imprinting template. The obtained catalyst is recyclable and exhibits a higher catalytic activity at a wider reaction temperature and pH due to the introduction of the polymer. This study provides a new approach to constructing enzyme mimics with customized substrate selectivity based on the peptide-based material platform.

研究领域: 生物化学 · 材料科学
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Biomaterials Science · 2019 ·Vol. 7 ·期 10 ·4142-4152 · IF 5.251

Construction, mechanism, and antibacterial resistance insight into polypeptide-based nanoparticles

Jian-Bin Zhen,Mu-Han Zhao,Ying Ge,Ya Liu,Li-Wei Xu,Cheng Chen,Yong-Kuan Gong,Ke-Wu Yang

The emergence of drug-resistant bacteria poses a serious threat to public health. The traditional antibiotics have specific intracellular targets and disinfect via chemical ways, which easily lead to the development of drug resistance, therefore, cationic peptides as promising antibiotic agents have attracted extensive attention due to their unique properties. Herein, we report a class of amphiphilic peptide-based pectinate polymers with primary amino groups. The polymers spontaneously self-assembled into the positively charged nanoparticles, which were evaluated and confirmed by scanning electron microscopy (SEM) and dynamic light scattering (DLS). Biological assays revealed that the nanoparticles showed broad-spectrum antibacterial efficacy against both Gram-positive and Gram-negative bacteria, exhibiting a MIC of 16 μg mL−1 against six clinical bacteria, namely, E. faecalis, S. aureus, MRSA, VRE, P. aeruginosa, and K. pneumonia, and three bacterial strains E. coli and E. coli producing NDM-1 and ImiS, and showed a sterilization rate of 95.6% and 94.7% on S. aureus and E. coli, respectively. Importantly, the nanoparticles did not result in drug-resistance for both the normal and drug-resistant bacteria tested after 14 passages and showed low toxicity on the mouse fibroblast cells (L929). The fluorescence staining, electrical conductivity, SEM, and surface plasmon resonance (SPR) characterization suggested that the nanoparticles initially bound to the surface of the bacteria, then pierced into the membranes of the bacteria with their phenyl groups, and finally disrupted the membranes, resulting in ions leaking out and thus exhibiting broad-spectrum antibacterial efficacy. This bactericidal mechanism that the nanoparticles employed does not lead the bacteria susceptible to developing drug resistance. This study provides a promising pathway for the development of the efficient antibacterial materials.

研究领域: 生物材料学 · 微生物学 · 药理学
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CHIRALITY · 2023 ·Vol. 35 ·期 9 ·636-644 · IF 2

Preparation and chromatographic performance of chiral peptide-based stationary phases for enantiomeric separation

Zhengyue Ma,Panpan Shang,Delu Liu,Yangyang Nie,Yanli Liu,Xinyuan Guo,Benben Wei,Ligai Bai,Xiaoqiang Qiao

This study presents the development of three new chiral stationary phases. They are based on silica modified with peptides containing phenylalanine and proline. Successful analyses and characterizations were conducted using Fourier transform infrared spectra, elemental analysis, and thermogravimetric analysis. After this, the enantioselective performance of the three chiral peptide-based columns was evaluated. The evaluation used 11 racemic compounds under normal-phase high performance liquid chromatography mode. Optimized enantiomeric separation conditions were established. Under these conditions, the enantiomers of flurbiprofen and naproxen were successfully separated on CSP-1 column: the separation factor of these was 1.27 and 1.21, respectively. In addition, the reproducibility of the CSP-1 column was also investigated. The results of the investigation illustrated that the stationary phases have good reproducibility (RSD = 0.73%, n = 5).

CAS / MDL: 13822-56-5
研究领域: 分析化学 · 药物化学
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