Cell selectivity and anti-inflammatory activity of a Leu/Lys-rich α-helical model antimicrobial peptide and its diastereomeric peptides

Wang, Peng; Nan, Yong Hai; Yang, Seun-Ah; Kang, Shin Won; Kim, Yangmee; Park, Il‐Seon; Hahm, Kyung‐Soo; Shin, Song Yub

doi:10.1016/j.peptides.2010.03.032

Cited by 32 publications

(31 citation statements)

References 36 publications

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“…Thus, many cAMPs cannot discriminate between eukaryotic and prokaryotic cells. Several efforts have been made to improve the cellular selectivity of cAMPs, including the optimization of physicochemical parameters (5,18,27,38,43). It is believed that high hydrophobicity and helicity are correlated with this selectivity (6,38).…”

Section: Resultsmentioning

confidence: 99%

“…Several efforts have been made to improve the cellular selectivity of cAMPs, including the optimization of physicochemical parameters (5,18,27,38,43). It is believed that high hydrophobicity and helicity are correlated with this selectivity (6,38). In addition, the self-association (oligomerization) of cAMPs in an aqueous environment is also known to be important for controlling the selectivity of the cAMPs (6,44).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, selected strategies have been performed to improve peptide stability, efficacy, delivery, and selectivity (10,21,27,32,34,38,45). As the plasma membrane is the target for cAMPs, selectivity is important and is responsible for their cytotoxicity to human cells.…”

mentioning

confidence: 99%

“…We have also shown that the N-terminal region is important for the hemolytic activity of synthetic peptides containing sequences from the N termini of sticholysins (7) and for selectivity of the cAMPs (10). Therefore, efforts have been undertaken to improve the selectivity of cAMPs, including sequence modification to optimize their physicochemical parameters (18,27,38,43).…”

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confidence: 99%

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Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

Lorenzón

Cespedes

Vicente

et al. 2012

Antimicrob Agents Chemother

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It is well known that cationic antimicrobial peptides (cAMPs) are potential microbicidal agents for the increasing problem of antimicrobial resistance. However, the physicochemical properties of each peptide need to be optimized for clinical use. To evaluate the effects of dimerization on the structure and biological activity of the antimicrobial peptide Ctx-Ha, we have synthesized the monomeric and three dimeric (Lys-branched) forms of the Ctx-Ha peptide by solid-phase peptide synthesis using a combination of 9-fluorenylmethyloxycarbonyl (Fmoc) and t-butoxycarbonyl (Boc) chemical approaches. The antimicrobial activity assay showed that dimerization decreases the ability of the peptide to inhibit growth of bacteria or fungi; however, the dimeric analogs displayed a higher level of bactericidal activity. In addition, a dramatic increase (50 times) in hemolytic activity was achieved with these analogs. Permeabilization studies showed that the rate of carboxyfluorescein release was higher for the dimeric peptides than for the monomeric peptide, especially in vesicles that contained sphingomyelin. Despite different biological activities, the secondary structure and pore diameter were not significantly altered by dimerization. In contrast to the case for other dimeric cAMPs, we have shown that dimerization selectively decreases the antimicrobial activity of this peptide and increases the hemolytic activity. The results also show that the interaction between dimeric peptides and the cell wall could be responsible for the decrease of the antimicrobial activity of these peptides.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

Lorenzón

Cespedes

Vicente

et al. 2012

Antimicrob Agents Chemother

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“…Moreover, chymotrypsin and elastase, which are proteases synthesized by pancreatic acinar cells and secreted in the small intestine [109], are responsible for cleaving peptide bonds in hydrophobic (phenylalanine, tryptophan, and tyrosine) and small amino acids (alanine, glycine, and valine), respectively [110]. To overcome the proteolytic cleavage of peptides, several trials have been conducted to evaluate the following: substitution of L-amino acids by d -amino acids [111,112], cyclization [113,114], conjugation of fatty acids [115], substitution by peptoids [116,117], use of fluorinated amino acids [118], beta-peptide [119], and acylation [120]. As novel candidates, although lantibiotics were mostly employed in food preservation, type-B is another prospective candidate in biomedical application against infections of MDR bacteria due to its resistance to proteolytic degradation [51].…”

Section: In Vivo Application Of Antimicrobial Peptidesmentioning

confidence: 99%

The Role of Antimicrobial Peptides in Preventing Multidrug-Resistant Bacterial Infections and Biofilm Formation

Park

Hahm

2011

IJMS

Self Cite

262

185

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Over the last decade, decreasing effectiveness of conventional antimicrobial-drugs has caused serious problems due to the rapid emergence of multidrug-resistant pathogens. Furthermore, biofilms, which are microbial communities that cause serious chronic infections and dental plaque, form environments that enhance antimicrobial resistance. As a result, there is a continuous search to overcome or control such problems, which has resulted in antimicrobial peptides being considered as an alternative to conventional drugs. Antimicrobial peptides are ancient host defense effector molecules in living organisms. These peptides have been identified in diverse organisms and synthetically developed by using peptidomimic techniques. This review was conducted to demonstrate the mode of action by which antimicrobial peptides combat multidrug-resistant bacteria and prevent biofilm formation and to introduce clinical uses of these compounds for chronic disease, medical devices, and oral health. In addition, combinations of antimicrobial peptides and conventional drugs were considered due to their synergetic effects and low cost for therapeutic treatment.

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Host defense peptides: An alternative as antiinfective and immunomodulatory therapeutics

2012

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Host defense peptides are conserved components of innate immune response present among all classes of life. These peptides are potent, broad spectrum antimicrobial agents with potential as novel therapeutic compounds. Also, the ability of host defense peptides to modulate immunity is an emerging therapeutic concept since its selective modulation is a novel antiinfective strategy. Their mechanisms of action and the fundamental differences between pathogens and host cells surfaces mostly lead to a not widely extended microbial resistance and to a lower toxicity toward host cells. Biological libraries and rational design are novel tools for developing such molecules with promising applications as therapeutic drugs.

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Cell selectivity and anti-inflammatory activity of a Leu/Lys-rich α-helical model antimicrobial peptide and its diastereomeric peptides

Cited by 32 publications

References 36 publications

Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

The Role of Antimicrobial Peptides in Preventing Multidrug-Resistant Bacterial Infections and Biofilm Formation

Host defense peptides: An alternative as antiinfective and immunomodulatory therapeutics

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