Antimicrobial activity and self-assembly behavior of antimicrobial peptide chensinin-1b with lipophilic alkyl tails

An increasing number of multidrug-resistant pathogens is a serious problem of modern medicine and new antibiotics are highly demanded. In this study, different n-alkyl acids (C2-C14) and aromatic acids (benzoic and trans-cinnamic) were conjugated to the N-terminus of KR12 amide. The effect of this modification on antimicrobial activity (ESKAPE bacteria and biofilm of Staphylococcus aureus) and cytotoxicity (human red blood cells and HaCaT cell line) was examined. The effect of lipophilic modifications on helicity was studied by CD spectroscopy, whereas peptide self-assembly was studied by surface tension measurements and NMR spectroscopy. As shown, conjugation of the KR12-NH2 peptide with C4-C14 fatty acid chains enhanced the antimicrobial activity with an optimum demonstrated by C8-KR12-NH2 (MIC 1–4 μg/mL against ESKAPE strains; MBEC of S. aureus 4–16 μg/mL). Correlation between antimicrobial activity and self-assembly behavior of C14-KR12-NH2 and C8-KR12-NH2 has shown that the former self-assembled into larger aggregated structures, which reduced its antimicrobial activity. In conclusion, N-terminal modification can enhance antimicrobial activity of KR12-NH2; however, at the same time, the cytotoxicity increases. It seems that the selectivity against pathogens over human cells can be achieved through conjugation of peptide N-terminus with appropriate n-alkyl fatty and aromatic acids.

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Comparison of a Short Linear Antimicrobial Peptide with Its Disulfide-Cyclized and Cyclotide-Grafted Variants against Clinically Relevant Pathogens

Microorganisms ◽

10.3390/microorganisms9061249 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1249

Author(s):

Johannes Koehbach ◽

Jurnorain Gani ◽

Kai Hilpert ◽

David J Craik

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptide ◽

Human Serum ◽

World Health ◽

Resistant Bacteria ◽

Moderate Activity ◽

Antimicrobial Compounds ◽

Strong Activity ◽

Linear Peptide ◽

Linear Version

According to the World Health Organization (WHO) the development of resistance against antibiotics by microbes is one of the most pressing health concerns. The situation will intensify since only a few pharmacological companies are currently developing novel antimicrobial compounds. Discovery and development of novel antimicrobial compounds with new modes of action are urgently needed. Antimicrobial peptides (AMPs) are known to be able to kill multidrug-resistant bacteria and, therefore, of interest to be developed into antimicrobial drugs. Proteolytic stability and toxicities of these peptides are challenges to overcome, and one strategy frequently used to address stability is cyclization. Here we introduced a disulfide-bond to cyclize a potent and nontoxic 9mer peptide and, in addition, as a proof-of-concept study, grafted this peptide into loop 6 of the cyclotide MCoTI-II. This is the first time an antimicrobial peptide has been successfully grafted onto the cyclotide scaffold. The disulfide-cyclized and grafted cyclotide showed moderate activity in broth and strong activity in 1/5 broth against clinically relevant resistant pathogens. The linear peptide showed superior activity in both conditions. The half-life time in 100% human serum was determined, for the linear peptide, to be 13 min, for the simple disulfide-cyclized peptide, 9 min, and, for the grafted cyclotide 7 h 15 min. The addition of 10% human serum led to a loss of antimicrobial activity for the different organisms, ranging from 1 to >8-fold for the cyclotide. For the disulfide-cyclized version and the linear version, activity also dropped to different degrees, 2 to 18-fold, and 1 to 30-fold respectively. Despite the massive difference in stability, the linear peptide still showed superior antimicrobial activity. The cyclotide and the disulfide-cyclized version demonstrated a slower bactericidal effect than the linear version. All three peptides were stable at high and low pH, and had very low hemolytic and cytotoxic activity.

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Evaluating the effects of hydrophobic and cationic residues on antimicrobial peptide self-assembly

Soft Matter ◽

10.1039/d1sm00096a ◽

2021 ◽

Vol 17 (16) ◽

pp. 4445-4451

Author(s):

Fengyi Cao ◽

Gangqing Ma ◽

Meng Song ◽

Genxing Zhu ◽

Lin Mei ◽

...

Keyword(s):

Antimicrobial Peptide ◽

Self Assembly ◽

Peptide Derivatives ◽

Cationic Residues ◽

Secondary Conformation

Four PAF26 peptide derivatives were used to study the effects of hydrophobic and cationic residues on self-assembly behaviours. It was found that peptide with different number of hydrophobic and cationic residues had different secondary conformation and microstructure.

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Self-Assembly of Single Chain Janus Nanoparticles from Azobenzene-Containing Block Copolymers and Reversible Photoinduced Morphology Transition

Polymer Chemistry ◽

10.1039/d1py00223f ◽

2021 ◽

Author(s):

Wei Wen ◽

Aihua Chen

Keyword(s):

Block Copolymers ◽

Experimental Research ◽

Self Assembly ◽

The Self ◽

Single Chain ◽

Morphology Transition ◽

Janus Nanoparticles ◽

Assembly Behavior

Self-assembly of amphiphilic single chain Janus nanoparticles (SCJNPs) is a novel and promising approach to fabricate assemblies with diversified morphologies. However, the experimental research of the self-assembly behavior of SCJNPs...

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Investigating the structure and self-assembly behavior of starch-g-VAc in starch-based adhesive by combining NMR analysis and multi-scale simulation

Carbohydrate Polymers ◽

10.1016/j.carbpol.2020.116655 ◽

2020 ◽

Vol 246 ◽

pp. 116655

Author(s):

Lei Chen ◽

Zhouyi Xiong ◽

Hanguo Xiong ◽

Zia-ud Din

Keyword(s):

Self Assembly ◽

Nmr Analysis ◽

Multi Scale ◽

Assembly Behavior

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Self-Assembly Behavior and Optical Properties of Poly(3-thiopheneacetate)/Dialkyldimethylammonium Complexes

Macromolecular Chemistry and Physics ◽

10.1002/macp.200900109 ◽

2009 ◽

Vol 210 (18) ◽

pp. 1510-1518 ◽

Cited By ~ 6

Author(s):

Young-Sik Yoon ◽

Kwang-Han Park ◽

Jong-Chan Lee

Keyword(s):

Optical Properties ◽

Self Assembly ◽

Assembly Behavior

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The macroscopic shape of assemblies formed from microparticles based on host–guest interaction dependent on the guest content

Scientific Reports ◽

10.1038/s41598-021-85816-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Takahiro Itami ◽

Akihito Hashidzume ◽

Yuri Kamon ◽

Hiroyasu Yamaguchi ◽

Akira Harada

Keyword(s):

Molecular Recognition ◽

Smart Materials ◽

Self Assembly ◽

Early Stage ◽

Contact Point ◽

Sodium Acrylate ◽

Contact Points ◽

Assembly Behavior ◽

Small Clusters ◽

Macroscopic Shape

AbstractBiological macroscopic assemblies have inspired researchers to utilize molecular recognition to develop smart materials in these decades. Recently, macroscopic self-assemblies based on molecular recognition have been realized using millimeter-scale hydrogel pieces possessing molecular recognition moieties. During the study on macroscopic self-assembly based on molecular recognition, we noticed that the shape of assemblies might be dependent on the host–guest pair. In this study, we were thus motivated to study the macroscopic shape of assemblies formed through host–guest interaction. We modified crosslinked poly(sodium acrylate) microparticles, i.e., superabsorbent polymer (SAP) microparticles, with β-cyclodextrin (βCD) and adamantyl (Ad) residues (βCD(x)-SAP and Ad(y)-SAP microparticles, respectively, where x and y denote the mol% contents of βCD and Ad residues). Then, we studied the self-assembly behavior of βCD(x)-SAP and Ad(y)-SAP microparticles through the complexation of βCD with Ad residues. There was a threshold of the βCD content in βCD(x)-SAP microparticles for assembly formation between x = 22.3 and 26.7. On the other hand, the shape of assemblies was dependent on the Ad content, y; More elongated assemblies were formed at a higher y. This may be because, at a higher y, small clusters formed in an early stage can stick together even upon collisions at a single contact point to form elongated aggregates, whereas, at a smaller y, small clusters stick together only upon collisions at multiple contact points to give rather circular assemblies. On the basis of these observations, the shape of assembly formed from microparticles can be controlled by varying y.

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