Effects of ferrocene position isomerization on the self-assembly behavior and antibacterial effect of coupled cationic peptides

LI Yijie; WANG Jingwen

doi:10.6039/j.issn.1001-0408.2023.18.10

您当前的位置：

首页 >

文章列表页 >

Effects of ferrocene position isomerization on the self-assembly behavior and antibacterial effect of coupled cationic peptides

更新时间：2025-09-26

- Effects of ferrocene position isomerization on the self-assembly behavior and antibacterial effect of coupled cationic peptides
- ZHONGGUO YAOFANG Vol. 34, Issue 18, Pages: 2226-2232(2023)
- 作者机构：
  
  1.上海交通大学药学院，上海　201100
  2.空军军医大学西京医院药剂科，西安　710038
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.18.10
  CLC： R978.1+6
- Received：07 February 2023，
  
  Revised：2023-03-19，
  
  Accepted：27 April 2023，
  
  Published：30 September 2023
- 稿件说明：
移动端阅览
李奕捷,王婧雯.二茂铁位置异构对偶联阳离子多肽自组装行为及其抗菌效果的影响[J].中国药房,2023,34(18):2226-2232.

LI Yijie,WANG Jingwen.Effects of ferrocene position isomerization on the self-assembly behavior and antibacterial effect of coupled cationic peptides[J].ZHONGGUO YAOFANG,2023,34(18):2226-2232.
李奕捷,王婧雯.二茂铁位置异构对偶联阳离子多肽自组装行为及其抗菌效果的影响[J].中国药房,2023,34(18):2226-2232. DOI： 10.6039/j.issn.1001-0408.2023.18.10.

LI Yijie,WANG Jingwen.Effects of ferrocene position isomerization on the self-assembly behavior and antibacterial effect of coupled cationic peptides[J].ZHONGGUO YAOFANG,2023,34(18):2226-2232. DOI： 10.6039/j.issn.1001-0408.2023.18.10.

摘要

目的

设计二茂铁（Fc）偶联阳离子多肽（以下简称“多肽”）的2种同分异构多肽[Fc-K（C

）FFHK、C

-K（Fc）FFHK

]

以及对照多肽[C

-K（C

）FFHK

]

，探究Fc位置异构对多肽自组装行为及其抗菌效果的影响。

方法

采用标准固相合成法合成位置异构的多肽，采用反相高效液相色谱法进行纯化；采用紫外可见分光光度法检测紫外吸收光谱，Zeta电位分析仪测定Zeta电位以分析多肽的稳定性；采用圆二色光谱（CD）、傅里叶红外光谱（FTIR）、硫代黄素T（ThT）荧光光谱、透射电子显微镜（TEM）等进行二级结构表征；通过体外活性氧（ROS）生成效率实验、生长曲线法测定实验、平板法实验、细胞毒性实验和溶血性实验评价2种同分异构多肽在抗菌活性和生物相容性上的差异。

结果

合成了3种纯度均高于95%的多肽。稳定性实验结果显示，室温下放置24、96 h时，Fc-K（C

）FFHK、C

-K（Fc）FFHK的紫外吸收图谱几乎没有改变，二者的Zeta电位分别减少了0.3、0.5 mV。二级结构表征结果显示，Fc-K（C

）FFHK、C

-K（Fc）FFHK分别自组装成扭曲纳米带和短纳米纤维结构，C

-K（C

）FFHK自组装成圆柱状纳米纤维结构；光学图谱结果显示，3种多肽的

-折叠、

-螺旋等结构含量具有一定差异。体外ROS生成实验结果显示，Fc-K（C

）FFHK在pH 6.0时的ROS生成效率高于C

-K（Fc）FFHK。体外抗菌活性结果显示，对于耐甲氧西林金黄色葡萄球菌，2种同分异构多肽的最低抑菌浓度（MIC）值均为50 μg/mL，远低于对照多肽的MIC值（400 μg/mL）；对于大肠杆菌，Fc-K（C

）FFHK的抗菌活性优于C

-K（Fc）FFHK。细胞毒性实验和溶血性实验均结果显示，2种同分异构多肽均具有较好的生物相容性。

结论

通过偶联Fc，能够提高多肽的抗菌活性；调节Fc在多肽序列中的位置，可调控多肽的自组装行为和抗菌效果。

Abstract

OBJECTIVE

To design the two isomers of ferrocene （Fc）-coupled cationic peptides （hereinafter referred to as “peptides”） [Fc-K（C

）FFHK and C

-K（Fc） FFHK

]

and the control peptide [C

-K（C

）FFHK

]

， and to explore the effects of Fc position isomerization on the self-assembly behavior and antibacterial effect of peptides.

METHODS

All isomerized peptides were prepared by standard solid-phase synthesis and purified by reversed-phase high-performance liquid chromatography. The stability of the peptide was analyzed by using UV spectrophotometry to detect UV absorption spectra， and Zeta potential analyzer to determine Zeta potential. The secondary structure was characterized by circular dichroism spectrum （CD）， Fourier transform infrared spectrometer （FTIR）， thioflavin T （ThT） fluorescence spectrum and transmission electron microscopy （TEM）. The differences in antibacterial activity and biocompatibility of the 2 kinds of isomerized peptides were evaluated by

in vitro

reactive oxygen species （ROS） generation test， growth curve determination test， plate method， cytotoxicity assay and hemolysis test.

RESULTS

Three peptides with purity higher than 95% were synthesized. The stability test results showed that the UV absorption spectra of Fc-K（C

）FFHK and C

-K（Fc）FFHK remained almost unchanged when placed at room temperature for 24 and 96 hours， and their Zeta potential were decreased by 0.3 mV and 0.5 mV， respectively. Secondary structure characterization results showed that Fc-K（C

）FFHK and C

-K（Fc）FFHK were self-assembled to form twisted nanoribbons and short nanofibers， respectively； C

-K（C

）FFHK was assembled into cylindrical nanofibers. The optical spectrum results showed that there were certain differences in the content of structures such as

-sheet and

-helix. The

in vitro

ROS generation test results showed that ROS generation efficiency of Fc-K（C

）FFHK at pH 6.0 was higher than C

-K（Fc）FFHK. The results of

in vitro

antibacterial activity showed that for methicillin-resistant

Staphylococcus aureus

， both the isomeric peptides had similar minimum inhibitory concentration （MIC） values of 50 μg/mL which were f

ar lower than the control peptide （400 μg/mL）. To

Escherichia coli

， Fc-K（C

）FFHK had better antibacterial activity than C

-K（Fc）FFHK. Finally， cytotoxicity assay and hemolysis test results showed that both isomeric peptides had good biocompatibility.

CONCLUSIONS

By coupling Fc， the antibacterial activity of cationic self-assembled peptides can be improved. Regulating the position of Fc in the peptide sequence could regulate the self-assembly behavior and antibacterial effect of the self-assembled peptides.

关键词

Keywords

references

PIDDOCK L J V . Reflecting on the final report of the O’Neill review on antimicrobial resistance [J ] . Lancet Infect Dis ， 2016 ， 16 （ 7 ）： 767 - 768 .

DAVIES J ， DAVIES D . Origins and evolution of anti-biotic resistance [J ] . Microbiol Mol Biol Rev ， 2010 ， 74 （ 3 ）： 417 - 433 .

LUO Y ， SONG Y Z . Mechanism of antimicrobial peptides：antimicrobial，anti-inflammatory and antibiofilm activities [J ] . Int J Mol Sci ， 2021 ， 22 （ 21 ）： 11401 .

KARDANI K ， BOLHASSANI A . Antimicrobial/anticancer peptides：bioactive molecules and therapeutic agents [J ] . Immunotherapy ， 2021 ， 13 （ 8 ）： 669 - 684 .

MELO M N ， FERRE R ， CASTANHO M A R B . Anti-microbial peptides：linking partition，activity and high membrane-bound concentrations [J ] . Nat Rev Microbiol ， 2009 ， 7 （ 3 ）： 245 - 250 .

LI X S ， BAI H T ， YANG Y C ， et al . Supramolecular antibacterial materials for combatting antibiotic resistance [J ] . Adv Mater ， 2019 ， 31 （ 5 ）： e1805092 .

CRAIK D J ， FAIRLIE D P ， LIRAS S ， et al . The future of peptide-based drugs [J ] . Chem Biol Drug Des ， 2013 ， 81 （ 1 ）： 136 - 147 .

ZHANG X Y ， ZHAO Y Q ， ZHANG Y D ， et al . Antimicrobial peptide-conjugated hierarchical antifouling polymer brushes for functionalized catheter surfaces [J ] . Biomacromolecules ， 2019 ， 20 （ 11 ）： 4171 - 4179 .

KUANG F ， CHEN Y J ， SHAN W ， et al . Biomimetic FeCo@PDA nanozyme platform with Fenton catalytic activity as efficient antibacterial agent [J ] . J Mater Chem B ， 2022 ， 10 （ 29 ）： 5582 - 5593 .

王迎军，黄雪连，陈军建，等 . 细菌感染微环境响应性高分子材料用于细菌感染性疾病的治疗 [J ] . 材料导报， 2019 ， 33 （ 1 ）： 8 - 18 .

MA Z Y ， LIU X H ， NIE J L ， et al . Nano-antimicrobial peptides based on constitutional isomerism-dictated self-assembly [J ] . Biomacromolecules ， 2022 ， 23 （ 3 ）： 1302 - 1313 .

ZHAO Y R ， WANG J Q ， DENG L ， et al . Tuning the self-assembly of short peptides via sequence variations [J ] . Langmuir ， 2013 ， 29 （ 44 ）： 13457 - 13464 .

SAHOO J K ， NAZARETH C ， VANDENBERG M A ， et al . Aromatic identity，electronic substitution，and sequence in amphiphilic tripeptide self-assembly [J ] . Soft Matter ， 2018 ， 14 （ 45 ）： 9168 - 9174 .

LIANG C ， BI X Y ， GAN K S ， et al . Short peptides derived from a block copolymer-like barnacle cement protein self-assembled into diverse supramolecular structures [J ] . Biomacromolecules ， 2022 ， 23 （ 5 ）： 2019 - 2030 .

XIE Y Y ， QIN X T ， ZHANG J X ， et al . Self-assembly of peptide nanofibers with chirality-encoded antimicrobial activity [J ] . J Colloid Interface Sci ， 2022 ， 622 ： 135 - 146 .

DEMBEK M ， BOCIAN S ， BUSZEWSKI B . Solvent influence on Zeta potential of stationary phase-mobile phase interface [J ] . Molecules ， 2022 ， 27 （ 3 ）： 968 .

FERREYRA MAILLARD A P V ， ESPECHE J C ， MATURANA P ， et al . Zeta potential beyond materials science：applications to bacterial systems and to the develop-ment of novel antimicrobials [J ] . Biochim Biophys Acta Biomembr ， 2021 ， 1863 （ 6 ）： 183597 .

TAN A ， XU F S ， YOKOYAMA C ， et al . Design，syn-thesis，and evaluation of the self-assembled antimicrobial peptides based on the ovalbumin-derived peptide TK913 [J ] . J Pept Sci ， 2022 ， 28 （ 4 ）： e3375 .

GONG Z Y ， SHI Y Y ， TAN H N ， et al . Plasma amine oxidase-induced nanoparticle-to-nanofiber geometric transformation of an amphiphilic peptide for drug encapsulation and enhanced bactericidal activity [J ] . ACS Appl Mater Interfaces ， 2020 ， 12 （ 4 ）： 4323 - 4332 .

SONG J L ， LIU H ， LEI M ， et al . Redox-channeling polydopamine-ferrocene（PDA-fc）coating to confer context-dependent and photothermal antimicrobial activities [J ] . ACS Appl Mater Interfaces ， 2020 ， 12 （ 7 ）： 8915 - 8928 .

ZHANG S ， HOLMES T ， LOCKSHIN C ， et al . Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane [J ] . Proc Natl Acad Sci U S A ， 1993 ， 90 （ 8 ）： 3334 - 3338 .

ALBADA B ， METZLER-NOLTE N . Highly potent antibacterial organometallic peptide conjugates [J ] . Acc Chem Res ， 2017 ， 50 （ 10 ）： 2510 - 2518 .

CASTELLETTO V ， EDWARDS-GAYLE C J C ， HAMLEY I W ， et al . Peptide-stabilized emulsions and gels from an arginine-rich surfactant-like peptide with antimicrobial activity [J ] . ACS Appl Mater Interfaces ， 2019 ， 11 （ 10 ）： 9893 - 9903 .

Views

296

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

Address：8th Floor, Sihuan Building, No. 129 Daping Main Street, Yuzhong District, Chongqing, China Postal code：400042
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰