Rational Design of Tryptophan‐Rich Antimicrobial Peptides with Enhanced Antimicrobial Activities and Specificities

  title={Rational Design of Tryptophan‐Rich Antimicrobial Peptides with Enhanced Antimicrobial Activities and Specificities},
  author={Hui‐Yuan Yu and Kuo‐Chun Huang and Bak‐Sau Yip and Chih-Hsiang Tu and Heng-Li Chen and Hsi-Tsung Cheng and Jyawei Cheng},
Trp‐rich antimicrobial peptides play important roles in the host innate defense mechanism of many plants and animals. A series of short Trp‐rich peptides derived from the C‐terminal region of Bothrops asper myothoxin II, a Lys49 phospholipase A2 (PLA2), were found to reproduce the antimicrobial activities of their parent molecule. Of these peptides, KKWRWWLKALAKK—designated PEM‐2—was found to display improved activity against both Gram‐positive and Gram‐negative bacteria. To improve the… 

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There is a world-wide quest for development of new-generation antibiotics, due to the emergence of microbial pathogens that have developed resistance to the currently available antibiotics. The

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Poly-lysine peptidomimetics having potent antimicrobial activity without hemolytic activity

It was found that hydrophobicity, +5 charges of multiple Lys residues, hydrocarbon tail lengths and cyclohexyl group were crucial for antimicrobial activity and membrane depolarization, dye leakage, inner membrane permeability and time-killing kinetics revealed that bacterial-killing mechanism of peptidomimetics is different from the membrane-targeting AMPs.

In vitro properties of designed antimicrobial peptides that exhibit potent antipneumococcal activity and produces synergism in combination with penicillin

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Correlations between membrane immersion depth, orientation, and salt-resistance of tryptophan-rich antimicrobial peptides.

Novel Antimicrobial Peptides with High Anticancer Activity and Selectivity

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Solution Structure of a Novel Tryptophan-Rich Peptide with Bidirectional Antimicrobial Activity

It is determined that the solution structures of Pac-525 bound to membrane-mimetic sodium dodecyl sulfate (SDS) micelles and vesicles, suggesting that the antimicrobial activity ofPac-525 may be due to interactions with bacterial membranes.

Mutational analysis of the role of tryptophan residues in an antimicrobial peptide.

The results provide a basis for a refined structural model of pediocin-like bacteriocins and highlight the unique role that tryptophan residues can play in membrane-interacting peptides.

Origin of Low Mammalian Cell Toxicity in a Class of Highly Active Antimicrobial Amphipathic Helical Peptides*

A significant role for tryptophan is highlighted in promoting binding of amphipathic helical peptides to neutral bilayers, augmenting the arsenal of strategies to reduce mammalian toxicity in antimicrobial peptides.

Structure of the antimicrobial peptide tritrpticin bound to micelles: a distinct membrane-bound peptide fold.

The structure of tritrpticin bound to membrane-mimetic sodium dodecyl sulfate micelles has been determined using conventional two-dimensional NMR methods and it is determined that the tryptophan residues are inserted into the micelle and are partially protected from the effects of the soluble fluorescence quencher acrylamide.

Tryptophan-rich antimicrobial peptides: comparative properties and membrane interactions.

The results illustrate that cationic Trp-rich antimicrobial peptides preferentially disrupt large unilamellar vesicles with a net negative charge following their insertion into the interfacial region of the phospholipid bilayer.

Amphipathic, α‐helical antimicrobial peptides

This review considers alpha-helical, antimicrobial peptides from the point of view of six interrelated structural and physicochemical parameters that modulate their activity and specificity: sequence, size, structuring, charge, amphipathicity, and hydrophobicity.

Structure and Mechanism of Action of an Indolicidin Peptide Derivative with Improved Activity against Gram-positive Bacteria*

A cationic peptide with a unique structure and an ability to interact with membranes and to affect intracellular synthesis of proteins, RNA, and DNA is introduced.

Diversity of antimicrobial peptides and their mechanisms of action.