Drug Design Development and Therapy
·
2022
·
IF 4.319
Kamel S Ahmed,Shenhuan Liu,Jing Mao,Jie Zhang,Lipeng Qiu
Background The active-targeted drug delivery systems had attracted more and more attention to efficiently overcome multidrug resistance (MDR) in cancer treatments. The aim of the work was to develop a multifunctional nano-structured liposomal system for co-delivery of doxorubicin hydrochloride (DOX) and celecoxib (CEL) to overcome doxorubicin resistance in breast cancer.Methods A functional hybrid peptide (MTS-R8H3) with unique cellular penetrability, endo-lysosomal escape and mitochondrial targeting ability was successfully synthesized using solid phase synthesis technology. The peptide modified targeted liposomes (DOX/CEL-MTS-R8H3 lipo) for co-delivery of DOX and CEL were formulated to overcome the chemoresistance in MCF/ADR cells.Results DOX/CEL-MTS-R8H3 lipo showed nanosized shape and displayed high stability for one month. The cytotoxicity effect of the co-delivery of DOX and CEL through peptide modified liposomes had remarkable treatment efficacy on killing MCF/ADR cells. Targeted liposome exhibited greater cellular entry ability about 5.72-fold stronger than DOX solution. Moreover, as compared with unmodified liposomes, the presence of MTS-R8H3 peptide entity on liposome surface enhanced the mitochondrial-targeting ability and achieved effective reactive oxygen species (ROS) production with significant inhibition of P-gp efflux activity.Conclusion The study suggested that the DOX/CEL-MTS-R8H3 lipo is a promising strategy for overcoming drug resistance in breast cancer treatments with high targeting inhibition efficiency.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Guixiang Wang,Rui Han,Qun Li,Yinfeng Han,Xiliang Luo
An electrochemical sensing platform for biomarker detection in complex serum samples with unique long-term antifouling performance was constructed, based on newly designed multifunctional peptides containing anchoring, doping, linking, and antifouling sequences. The designed peptides were first attached onto an electrode surface with the assistance of the anchoring sequences, and the negatively charged doping sequences as dopants for conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) were then precisely doped into the electropolymerized PEDOT to form a conducting and stable substrate, leaving the linking and antifouling sequences exposed on the PEDOT substrate surface. The linking sequence of the peptide between the doping and antifouling parts was designed to be beneficial for enhancing the antifouling performance. After the biorecognizing probe immobilization, the obtained biosensor was able to detect targets with a low limit of detection of 2.3 fM and high specificity in complex biological fluids. More importantly, the electrochemical biosensor exhibited incomparable long-term antifouling performances over previous reports and retained their antifouling capabilities for 20 days, indicating a promising feasibility of this design strategy for the construction of biosensors and bioelectronics to be used or implanted in real biological systems.
研究领域:
生物传感技术
·
分子生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2018
·
IF 5.711
Nianzu Liu,Ni Hui,Jason J. Davis,Xiliang Luo
The construction of sensitive and selective biosensors capable of detecting specific targets in complex biological samples remains a challenge highly relevant to a range of sensor/diagnostic applications. Herein, we have utilized a multifunctional peptide to present an interface that supports the very specific recruitment of targets from serum. The novel peptide sequence designed contains an anchoring domain (CPPPP-), an antifouling domain (-NQNQNQNQDHWRGWVA), and a human immunoglobulin G (IgG) recognition domain (-HWRGWVA), and the whole peptide was designed to be antifouling. These were integrated into polyaniline nanowire arrays in supporting the quantification of IgG (with a limit of detection of 0.26 ng mL–1) in neat serum and real clinical samples. The strategy of utilizing multisegment peptide films to underpin highly selective target recruitment is, of course, readily extended to a broad range of targets for which an affinity sequence can be generated.
研究领域:
生物化学
·
诊断学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Qingyue Li,Xiya Zhang,Mengtian Chen,Changwei Luo,Ran Yang,Tong Bu,Meng Dang,Xianqing Huang,Lianjun Song,Pingan Zhang,Liang Liu,Yexuan Mao
To integrate antifouling properties and good sensitivity on the sensing interface can improve the applicability of an electrochemical immunosensor. These functional regions can be integrated into a single functional peptide (functPP). The rational designed three domains in functPP were the anchoring, antifouling and gold nanoparticles (AuNPs) recognizing domains. Meanwhile, the ordered AuNPs inspired by C 15 H 23 CO-RRRRR can be recognized by AuNPs recognizing domains in functPP to enhance the intensity of detecting current. In the sensing system, the anchoring domain in functPP can be immobilized on the Au electrode by Au S interaction, while the antifouling domain undergoes strong hydration with water molecules to resist matrices, and the recognizing domains can directionally capture O-AuNPs to form a functPP-O-AuNPs complex as the core sensing element. Consequently, the complex bound to the monoclonal antibodies against zearalenone by electrostatic adsorption to develop a highly antifouling and sensitive biosensor with the ability to identify zearalenone in cereals.
研究领域:
分析化学
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生物传感
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食品安全检测
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
·
2025
·Vol. 31
·期 15
·e202404349
·
IF 3.7
Lujuan Yang,Yao Wang,Peng Shang,Gang Ma
Graphical This study presented two strategies to aid in the discovery of synthetic peptide inhibitors with anti-amyloid and antimicrobial activities for Alzheimer's disease. Four synthetic peptides were identified, including the shortest linear peptide and two cyclic peptides with simple structures. Dual-functional peptides exhibiting both anti-amyloid and antimicrobial activities have attracted attention as promising candidates for Alzheimer's disease treatment. The advantage of these peptides lies in their ability to simultaneously target both the amyloid cascade hypothesis and the microbial infection hypothesis, in contrast to single-function inhibitors. However, most of the reported dual-functional peptides to date are natural peptides, and the development of synthetic peptides in this area remains limited. In this study, we propose two strategies to aid in the discovery of synthetic dual-functional peptides. We then report four distinct synthetic dual-functional peptides identified using these strategies, with the Aβ 1–40 /Aβ 1–42 fibrillation system and common bacterial strains serving as a proof-of-concept platform. One strategy involves repurposing existing knowledge, while the other breaks from established conventions. Using the first strategy, we discovered a very short dual-functional linear peptide. With the second strategy, we identified a simple dual-functional cyclic peptide. Furthermore, by combining these two strategies, we developed a hybrid dual-functional peptide incorporating both linear and cyclic structures. We hope that our findings will contribute to the future discovery of more synthetic dual-functional peptides for treating Alzheimer's disease.
研究领域:
生物化学
·
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Qian Zhou,Dankui Liao,Yongfang Xu,Lei Wang,Lixia Sun,Jianhua Sun,Xiongdiao Lan,Zhangfa Tong,Guangzhi Zhou
From the perspective of functional food development, an in-depth study of the interaction between food-derived angiotensin-converting enzyme inhibitory peptides (ACEIPs) and serum albumin is crucial for understanding their physicochemical stability after absorption within the body. Thus, this study explored the interaction mechanisms of bovine serum albumin (BSA) with bonito sauce-derived ACEIP Ala-Gly-Pro (AGP) using biosafety, biophysics, and computational biology. The results indicated that AGP demonstrated good biosafety, and competitively inhibited ACE activity (500 ± 24 μmol/L). Multi-spectroscopic and isothermal titration calorimetry analysis proved that AGP could spontaneously insert in the site I of BSA and form a non-covalent complex, clearly changing the structure and microenvironment of BSA. Molecular docking and molecular dynamics simulations successfully revealed the dynamic conformational changes and non-covalent interactions in the BSA–AGP complex. These findings provide valuable data on food-derived ACEIP AGP, serving as a reference and model for studying similar peptides in developing antihypertensive functional foods.
研究领域:
生物化学
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分子生物学
·
食品科学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 9
·期 1
·1901229
·
IF 6.27
Shi-Zhao Lu,Xiao-Yan Guo,Mei-Shuai Zou,Zi-Qin Zheng,Yu-Chuan Li,Xiao-Dong Li,Li-Li Li,Hao Wang
The emergence of drug-resistant bacteria is becoming the focus of global public health. Early-stage pathogen bioimaging will offer a unique perspective to obtain infection information in patients. A photoacoustic (PA) contrast agent based on functional peptide modified gold nanoparticles (AuNPs@P1) is developed. These nanoparticles can be specifically tailored surface peptides by bacterial overexpressed enzyme inducing in situ aggregation of the gold nanoparticles. In the meantime, the close aggregation based on the hydrogen bonding, π–π stacking, and hydrophobic interaction of the peptide residues on the surface of gold nanoparticles exhibits a typical redshifted and broadened plasmon band. In addition, this active targeting and following in situ stimuli-induced aggregation contribute to increased nanoparticle accumulation in the infected site. Finally, the dynamic aggregation of AuNPs@P1 results in dramatically enhanced photoacoustic signals for bioimaging bacterial infection in vivo with high sensitivity and specificity. It is envisioned that this PA contrast agent may provide a new approach for early detection of bacterial infection in vivo.
研究领域:
生物医学工程
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纳米技术
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医学成像
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yuping Wei,Man Zhang,Pengfei Jiao,Xin Zhang,Ganggang Yang,Xia Xu
In our pervious study, a dual-functional peptide R7 was developed to form a complex with paclitaxel (PTX) for enhancement of PTX translocation. However, because of the unstable noncovalent bond between R7 and PTX, PTX redistributed after the introduction of heparin, leading to R7-PTX complex dissociation, further causing less PTX penetration than expected. Thus, a novel positive CPP carrier of P9 was developed to improve CPP-PTX affinity via a double-proline (Pro, P) hairpin tail and enhance PTX translocation through the reduction of translocation energy barrier, confirmed by the MM-PBSA analysis and umbrella sampling simulation. Cellular uptake study reveals that P9 can quickly translocate into the HeLa cells within 1 min and exhibits no noticeable cytotoxicity. Compared to R7, P9 is able to help PTX translocation, leading to a remarkable increase in the intracellular concentration of PTX, eventually resulting in a significant loss in tumor cell viability. In vivo experiments demonstrate that a vein injection of P9-PTX complex dramatically inhibits tumor growth. Our study provides a novel perspective for designing CPP-facilitated drug carrier to enhance antitumor efficiency.
研究领域:
药学
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生物技术
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癌症研究
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Quality and Safety
·
2024
·
IF 3
Zhang Rongbin,Zhou Zhilei,Ji Zhongwei,Ren Qingxi,Liu Shuangping,Xu Yuezheng,Mao Jian
Lees were the major by-product of Huangjiu brewing, and prone to decompose due to abundant protein residues. To convert the lees into high-value peptides with umami and antioxidant difunctional, herein, a one-step hydrolysis method combined with flavourzyme followed by amylase pretreatment was developed and optimized. The target peptide fraction was collected and evaluated after ultrafiltration and ethanol precipitation, then identified by nano-HPLC-MS/MS. The results show that 80U/g amylase and 3500U/g flavourzyme synergistic hydrolysis 50℃ for 3h performed best umami intensity and antioxidant activity. A total of 5266 peptides was identified from the 80% ethanol precipitation fraction, then filtered 7 umami peptides through virtual screening, sensory, and radical scavenging verification. The umami recognition threshold of 7 peptides ranged from 0.38 to 0.66 mmol/L at water. Among them, DPDGW and DNPNW exhibited well DPPH antioxidant ability with IC50 values of 0.6982 and 0.4315 mg/mL, respectively. Additionally, molecular docking studies indicated that all umami peptides tend to interact with the T1R3 receptor through hydrogen bonds and van der Waals forces, involving key residues such as ASN68, SER104, HIS145, SER276, VAL277, GLU301, ALA302, THR305, and HIS387. This research provides a reference for the flavor peptide resource development, oriented towards dual functionality in flavor and health.
研究领域:
食品科学
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生物化学
·
肽化学
·
风味化学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Mengdi Song,Zhou Fang,Jun Wang,Kehai Liu
Ovarian cancer (OC) has a low five-year survival rate, mainly because of its drug resistance to chemotherapy. It is the key to reverse drug resistance to combine multiple sensitization pathways to play a synergistic role. A nano scaled targeted co-delivery system (P123-PEI-G12, PPG) modified by bifunctional peptide tLyP-1-NLS (G12) was fabricated by using Pluronic P123 conjugated with low molecular weight polyethyleneimine (PEI). This delivery system can co-delivery Olaparib (Ola) and p53 plasmids to synergistically enhance the sensitivity of OC to platinum-based chemotherapy. [email protected] /Ola (Co-PPGs) can achieve efficient tumor accumulation and cellular internalization through G12-mediated targeting. Co-PPGs then break down in the tumor cells, releasing the drug. Co-PPGs significantly enhanced the sensitivity of cisplatin (DDP) in platinum-resistant ovarian cancer (PROC) and synergistically inhibited the proliferation of PROC in vitro and in vivo . The sensitizing and synergistic effects of Co-PPGs were related to the activation of p53, inhibition of poly-ADP-ribose polymerase (PARP) and p-glycoprotein (P-gp) expression. This work provides a promising strategy for the effective treatment of PROC.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
RSC Chemical Biology
·
2022
·Vol. 3
·期 10
·1276-1281
·
IF 0
Xuan Ding,Ziyi Wang,Bin Zheng,Shengchao Shi,Yibing Deng,Hanyang Yu,Peng Zheng
Enzymatic protein ligation has become the most powerful and widely used method for high-precision atomic force microscopy single-molecule force spectroscopy (AFM-SMFS) study of protein mechanics. However, this methodology typically requires the functionalization of the glass surface with a corresponding peptide sequence/tag for enzymatic recognition and multiple steps are needed. Thus, it is time-consuming and a high level of experience is needed for reliable results. To solve this problem, we simplified the procedure using two strategies both based on asparaginyl endopeptidase (AEP). First, we designed a heterobifunctional peptide-based crosslinker, GL-peptide-propargylglycine, which links to an N3-functionalized surface via the click reaction. Then, the target protein with a C-terminal NGL sequence can be immobilized via the AEP-mediated ligation. Furthermore, we took advantage of the direct ligation between primary amino in a small molecule and protein with C-terminal NGL by AEP. Thus, the target protein can be immobilized on an amino-functionalized surface via AEP in one step. Both approaches were successfully applied to the AFM-SMFS study of eGFP, showing consistent single-molecule results.
研究领域:
生物化学
·
生物物理学
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
MOLECULES
·
2024
·Vol. 29
·期 13
·3022
·
IF 4.2
Yuping Wei,Ziyang Liu,Man Zhang,Xingyan Zhu,Qiuhong Niu
Considering the high evolutionary rate and great harmfulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is imperative to develop new pharmacological antagonists. Human angiotensin-converting enzyme-2 (ACE2) functions as a primary receptor for the spike protein (S protein) of SARS-CoV-2. Thus, a novel functional peptide, KYPAY (K5), with a boomerang structure, was developed to inhibit the interaction between ACE2 and the S protein by attaching to the ACE2 ligand-binding domain (LBD). The inhibition property of K5 was evaluated via molecular simulations, cell experiments, and adsorption kinetics analysis. The molecular simulations showed that K5 had a high affinity for ACE2 but a low affinity for the cell membrane. The umbrella sampling (US) simulations revealed a significant enhancement in the binding potential of this functional peptide to ACE2. The fluorescence microscopy and cytotoxicity experiments showed that K5 effectively prevented the interaction between ACE2 and the S protein without causing any noticeable harm to cells. Further flow cytometry research indicated that K5 successfully hindered the interaction between ACE2 and the S protein, resulting in 78% inhibition at a concentration of 100 μM. This work offers an innovative perspective on the development of functional peptides for the prevention and therapy of SARS-CoV-2.
研究领域:
药理学
·
病毒学
·
分子生物学
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）