Central β-turn increases the cell selectivity of imperfectly amphipathic α-helical peptides

Shao, Changxuan; Tian, Haotian; Wang, Tianyu; Wang, Zhihua; Chou, Shuli; Shan, Anshan; Cheng, Baohua

doi:10.1016/j.actbio.2018.01.009

Cited by 66 publications

(72 citation statements)

References 53 publications

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“…The antibacterial activity of AMPs can be affected by many factors. Previous studies demonstrated that a proper positive charge (+6 to +7) was essential for antibacterial activity, but antibacterial activity was no longer increased when the positive charge of AMPs was beyond the threshold [17,20]. In this study, the positive charge of the designed peptides was set to +6.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the antibacterial activity of XR pG was higher than that of XR GG . Some papers confirmed that the rigid loop (pG), which promotes tightness in the hydrophobic center, has a better effect than the flexible loop (GG) [20].…”

Section: Discussionmentioning

confidence: 99%

“…Hydrophobic amino acids F, I, and L were used to damage microbial cell membranes [19]. Flexible (GG) and rigid (pG) loops were selectively inserted into the middle of two symmetric heptad repeat sequences to enhance cell selectivity [17,20]. In addition, Arg (R) was selectively introduced into the sequence template.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, Arg (R) was selectively introduced into the sequence template. The guanidine side chain of R allows it to form strong bidentate H-bonds with the phosphate moiety of lipid head groups, thereby enhancing the electrostatic action between peptides and anionic bacterial membranes [20]. To determine the role of loops in the designed peptides, a control peptide was designed as a heptad repeat sequence as follows: the central pG loop of peptide LR pG with highest cell selectivity was removed, and Leu located at the N-terminus and C-terminus of the peptide was exchanged with Gly and d-Pro, respectively.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

Jia

Wang

Zhang

et al. 2020

IJMS

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Antimicrobial peptides (AMPs) have a unique action mechanism that can help to solve global problems in antibiotic resistance. However, their low therapeutic index and poor stability seriously hamper their development as therapeutic agents. In order to overcome these problems, we designed peptides based on the sequence template XXRXXRRzzRRXXRXX-NH 2 , where X represents a hydrophobic amino acid like Phe (F), Ile (I), and Leu (L), while zz represents Gly-Gly (GG) or d-Pro-Gly (pG). Showing effective antimicrobial activity against Gram-negative bacteria and low toxicity, designed peptides had a tendency to form an α-helical structure in membrane-mimetic environments. Among them, peptide LR pG (X: L, zz: pG) showed the highest geometric mean average treatment index (GM TI = 73.1), better salt, temperature and pH stability, and an additive effect with conventional antibiotics. Peptide LR pG played the role of anti-Gram-negative bacteria through destroying the cell membrane. In addition, peptide LR pG also exhibited an anti-inflammatory activity by effectively neutralizing endotoxin. Briefly, peptide LR pG has the potential to serve as a therapeutic agent to reduce antibiotic resistance owing to its high therapeutic index and great stability.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

Jia

Wang

Zhang

et al. 2020

IJMS

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“…Although early isolation of many AMPs from natural sources, such as melittin, magainin, and cathelicidins, was promising as substitutes for antibiotics, there are still some obstacles to be solved in natural AMP, including long sequences, high toxicity, and poor antibacterial efficacy (Kim, Jang, Kim, & Cho, ; Ong, Wiradharma, & Yang, ). Therefore, numerous methods, such as de novo (Shao et al, ), sequence modification (truncation/substitution/hybridization; Lyu, Yang, Lyu, Dong, & Shan, ), synthetic combinatorial libraries, and template establishments (Li et al, ), have been developed for peptide design to solve and compensate for the innate deficiency. Additionally, all of these methods are based on analysis of common features of the peptide or systematic screening, such as cationicity, sequence, hydrophobicity, amphiphilicity, and structure, to obtain valuable contribution on the biological activity of the peptides for each parameter (Teixeira, Feio, & Bastos, ).…”

Section: Introductionmentioning

confidence: 99%

Effect of terminal arrangement of tryptophan on biological activity of symmetric α‐helix‐forming peptides

Shao

Lai

et al. 2019

Chem Biol Drug Des

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It is traditionally believed that the distribution of tryptophan (Trp) residues is critical for the novo design of antimicrobial peptides (AMPs). However, there is scarce knowledge regarding Trp residues arrangement at the head group level. Thus, a set of α‐helical AMPs containing different Trp residue arrangements at the N‐/C‐terminal of sequence were designed to increase the strategy database and analyze their biological activities. The arrangement of the N‐terminal Trp residue significantly improved the bacteriostatic activity of the peptides, but the C‐terminal Trp residue arrangement reduced the biocompatibility of them. WL and LW were effective against Gram‐negative microbes and had high selectivity for bacteria as compared to human erythrocytes and mammalian cells. They both maintained a relatively desirable activity in the presence of physiological salts and serum. It is observed through electron microscope, flow cytometry and fluorescence spectroscopy that target peptides can penetrate bacterial cell membrane and kill it by damaging cell membrane integrity. Collectively, we determined the structure–activity relationship of Trp residue distributions in a symmetric sequence structure and filled the gap in knowledge related to Trp arrangements at the head group level. The obtained results will be helpful in designing of artificial peptide‐based antimicrobials.

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pH‐Triggered Size‐Transformable and Bioactivity‐Switchable Self‐Assembling Chimeric Peptide Nanoassemblies for Combating Drug‐Resistant Bacteria and Biofilms

Tan

Tang

et al. 2023

Advanced Materials

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Drug‐resistant bacteria and biofilm‐associated infections are prominent problems in the field of antibacterial medicine, seriously affecting human and animal health. Despite the great potential of nanomaterials in the antibacterial field, overcoming the paradox of size and charge, efficient penetration, and retention within biofilms remain a formidable challenge. Here, self‐assembling chimeric peptide nanoassemblies composed of multiple functional fragments are designed for the treatment of drug‐resistant bacteria and biofilm‐associated infections. Notably, the chimeric peptide self‐assembles into nanofibers at pH 7.4 and is transformable into nanoparticles in the acidic biofilm‐infected microenvironment at pH 5.0, and thus achieves a size reduction and charge increase, improving the penetration into the bacterial biofilms and killing drug‐resistant bacteria by a mechanism dominated by membrane cleavage. In vivo mouse and piglet infection models confirm the ability of chimeric peptide nanoassemblies to reduce bacterial load within biofilms. Collectively, this research on pathological‐environment‐driven nanostructural transformations may provide a theoretical basis for designing high‐performance antibacterial nanomaterials and advance the application of peptide‐based nanomaterials in medicine and animal husbandry.

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Central β-turn increases the cell selectivity of imperfectly amphipathic α-helical peptides

Cited by 66 publications

References 53 publications

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

Effect of terminal arrangement of tryptophan on biological activity of symmetric α‐helix‐forming peptides

pH‐Triggered Size‐Transformable and Bioactivity‐Switchable Self‐Assembling Chimeric Peptide Nanoassemblies for Combating Drug‐Resistant Bacteria and Biofilms

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