2000
DOI: 10.1042/bj3470633
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Large-scale synthesis and functional elements for the antimicrobial activity of defensins

Abstract: Human neutrophil defensins, and their analogues incorporating anionic, hydrophobic or cationic residues at the N- and C-termini, were synthesized by solid-phase procedures. The synthetic defensins were examined for their microbicidal activity against Candida albicans, two Gram-negative bacteria (Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis) and two Gram-positive bacteria (Streptococcus gordonii and Streptococcus mutans). The human neutrophil peptide 1 (HNP1) and HNP2 were found to be poten… Show more

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Cited by 61 publications
(14 citation statements)
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“…These variations presumably account for their diversity in speci¢city and antimicrobial activity. The residues at the polar face are found to alter signi¢cantly the microbicidal potency and speci¢city of human neutrophil defensins [32]. This was demonstrated by the observation that the Gram-negative bacteria Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis and the Gram-positive bacteria Streptococcus gordonii and Streptococcus mutans are insensitive to human neutrophil defensins.…”
Section: Structure^function Correlationsmentioning
confidence: 99%
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“…These variations presumably account for their diversity in speci¢city and antimicrobial activity. The residues at the polar face are found to alter signi¢cantly the microbicidal potency and speci¢city of human neutrophil defensins [32]. This was demonstrated by the observation that the Gram-negative bacteria Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis and the Gram-positive bacteria Streptococcus gordonii and Streptococcus mutans are insensitive to human neutrophil defensins.…”
Section: Structure^function Correlationsmentioning
confidence: 99%
“…Analogs of human neutrophil defensins incorporating two additional cationic residues at the N-and C-terminals have been shown to exhibit high microbicidal potency against these organisms, suggesting the importance of the N-and Cterminal residues for microbicidal activity. The enhanced microbicidal activity observed for defensin analogs could be due to optimization of the amphiphilicity of the structure, facilitating speci¢c interactions with microbial membranes [32].…”
Section: Structure^function Correlationsmentioning
confidence: 99%
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“…This makes them particularly attractive as potential therapeutic agents, especially in view of the increasing problem of bacterial resistance to traditional antibiotics. The antimicrobial activity is especially sensitive to primary amino acid sequence; for example, the addition of two basic amino acids at the C-terminus and two hydrophobic amino acids to an a-defensin sequence resulted in peptides that were optimally active against several oral pathogens (27). Sequence variation is currently being explored to engineer therapeutic antimicrobial peptides, for example, in the treatment of oral mucositis (28).…”
Section: Antimicrobial Actionmentioning
confidence: 99%