Role of β-naphthylalanine end-tags in the enhancement of antiendotoxin activities: Solution structure of the antimicrobial peptide S1-Nal-Nal in complex with lipopolysaccharide

Yu, Huiyuan; Chen, Yi‐An; Yip, Bak-Sau; Wang, Siou-Ying; Wei, Hsiu-Ju; Chih, Ya-Han; Chen, Kuan-Hao; Cheng, Jya‐Wei

doi:10.1016/j.bbamem.2017.03.007

Cited by 16 publications

(13 citation statements)

References 63 publications

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“…Hydrophobicity was further modulated by insertion of aromatic residues, such as 2-naphthyl-L-alanine (2-Nal) and tryptophan. These residues have been already demonstrated to increase the antibacterial activity in various peptide sequences 43 , 44 . Finally, two side chain protected Cys residues, as thioether (CysS-tBu) or disulfide (Cys-S-S-ter-butyl-thio), were inserted into the sequences named SR or SS, respectively.…”

Section: Resultsmentioning

confidence: 93%

Exploring the role of unnatural amino acids in antimicrobial peptides

Oliva

Chino

Pane

et al. 2018

Sci Rep

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Cationic antimicrobial peptides (CAMPs) are a promising alternative to treat multidrug-resistant bacteria, which have developed resistance to all the commonly used antimicrobial, and therefore represent a serious threat to human health. One of the major drawbacks of CAMPs is their sensitivity to proteases, which drastically limits their half-life. Here we describe the design and synthesis of three nine-residue CAMPs, which showed high stability in serum and broad spectrum antimicrobial activity. As for all peptides a very low selectivity between bacterial and eukaryotic cells was observed, we performed a detailed biophysical characterization of the interaction of one of these peptides with liposomes mimicking bacterial and eukaryotic membranes. Our results show a surface binding on the DPPC/DPPG vesicles, coupled with lipid domain formation, and, above a threshold concentration, a deep insertion into the bilayer hydrophobic core. On the contrary, mainly surface binding of the peptide on the DPPC bilayer was observed. These observed differences in the peptide interaction with the two model membranes suggest a divergence in the mechanisms responsible for the antimicrobial activity and for the observed high toxicity toward mammalian cell lines. These results could represent an important contribution to unravel some open and unresolved issues in the development of synthetic CAMPs.

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Section: Resultsmentioning

confidence: 93%

Exploring the role of unnatural amino acids in antimicrobial peptides

Oliva

Chino

Pane

et al. 2018

Sci Rep

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“…The two terminal β-naphthylalanine residues of S1-Nal-Nal (Ac-KKWRKWLAKKNalNal-NH 2 ) were inserted into the hydrophobic lipid A motif of LPS micelles [6]. The extra hydrophobic interactions of S1-Nal-Nal then resulted in greater membrane permeabilization and translocation of the peptide into the membrane.…”

Section: Introductionmentioning

confidence: 99%

“…The extra hydrophobic interactions of S1-Nal-Nal then resulted in greater membrane permeabilization and translocation of the peptide into the membrane. Similarly, derivatives with phenylalanine-(Phe-P-113), β-naphthylalanine-(Nal-P-113), β-diphenylalanine-(Dip-P-113), and β-(4,4'-biphenyl)alanine-(Bip-P-113) substituted histidine-rich antimicrobial peptide P-113 (Ac-AKRHHGYKRKFH-NH 2 ) were developed [6,7]. Among these derivatives, Bip-P-113 displayed enhanced salt resistance, serum proteolytic stability, peptide-induced permeabilization, zeta potential measurements, LPS aggregation, and in vitro and in vivo LPS neutralizing activities [8].…”

Section: Introductionmentioning

confidence: 99%

“…We have developed a method to increase salt resistance, serum proteolytic stability, and LPS neutralizing activities of antimicrobial peptides by adding bulky non-nature amino acids to their termini [ 4 , 5 ]. The two terminal β-naphthylalanine residues of S1-Nal-Nal (Ac-KKWRKWLAKKNalNal-NH 2 ) were inserted into the hydrophobic lipid A motif of LPS micelles [ 6 ]. The extra hydrophobic interactions of S1-Nal-Nal then resulted in greater membrane permeabilization and translocation of the peptide into the membrane.…”

Section: Introductionmentioning

confidence: 99%

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Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli

Hsueh

Yip

et al. 2020

IJMS

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There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.

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“…Recently, solution structures of S1 (Ac-KKWRKWLAKK-NH 2 ) and S1-Nal-Nal (Ac-KKWRKWLAKKNal-Nal-NH 2 ) in complex with LPS micelles have been reported [37]. Both S1 and S1-Nal-Nal bound to LPS through the hydrophilic surface of their helices to the negatively charged region of LPS.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Peptides with Enhanced Salt Resistance and Antiendotoxin Properties

Chu

Chih

Peng

et al. 2020

IJMS

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A strategy was described to design antimicrobial peptides (AMPs) with enhanced salt resistance and antiendotoxin activities by linking two helical AMPs with the Ala-Gly-Pro (AGP) hinge. Among the designed peptides, KR12AGPWR6 demonstrated the best antimicrobial activities even in high salt conditions (NaCl ~300 mM) and possessed the strongest antiendotoxin activities. These activities may be related to hydrophobicity, membrane-permeability, and α-helical content of the peptide. Amino acids of the C-terminal helices were found to affect the peptide-induced permeabilization of LUVs, the α-helicity of the designed peptides under various LUVs, and the LPS aggregation and size alternation. A possible model was proposed to explain the mechanism of LPS neutralization by the designed peptides. These findings could provide a new approach for designing AMPs with enhanced salt resistance and antiendotoxin activities for potential therapeutic applications.

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Role of β-naphthylalanine end-tags in the enhancement of antiendotoxin activities: Solution structure of the antimicrobial peptide S1-Nal-Nal in complex with lipopolysaccharide

Cited by 16 publications

References 63 publications

Exploring the role of unnatural amino acids in antimicrobial peptides

Exploring the role of unnatural amino acids in antimicrobial peptides

Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli

Antimicrobial Peptides with Enhanced Salt Resistance and Antiendotoxin Properties

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