PGLa-H tandem-repeat peptides active against multidrug resistant clinical bacterial isolates

Rončević, Tomislav; Gajski, Goran; Ilić, Nada; Goić-Barišić, Ivana; Tonkić, Marija; Zoranić, Larisa; Simunić, Juraj; Benincasa, Monica; Mijaković, Marijana; Tossi, Alessandro; Juretić, Davor

doi:10.1016/j.bbamem.2016.11.011

Cited by 23 publications

(31 citation statements)

References 63 publications

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“…The presence of SDS micelles induced a transition from random coil to helical structures as indicated by the two minima at 222 nm and 209 nm and a maximum at 192 nm. The experiments performed at 298 K showed slightly higher intensities than at 323 K, especially for Kiadin, but overall the CD experiments did not show any significant difference in secondary structure content between both peptides, as previously reported 7 . Glycine is often reported as a helix-breaking residue due to its large conformational space of phi-psi angles and thus increased entropy of the backbone in the coil structure 9 .…”

Section: Kiadin and Dipgla-h Produced Similar CD Lineshapesupporting

confidence: 86%

Glycine Substitution Reduces Antimicrobial Activity and Helical Stretch of diPGLa-H in Lipid Micelles

et al. 2017

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With the rise in antibiotic resistance, antimicrobial peptides (AMPs) show promise for therapeutic development, but higher specificity is required. PGLa-H is a naturally occurring decapeptide, reported to have moderate antibacterial activity and low hemolytic activity, with its sequence being identical to that of the C-terminal fragment of highly selective AMP, PGLa. DiPGLa-H, a sequential tandem repeat of PGLa-H, and Kiadin, an analogue with a Val to Gly substitution at position 15, display improved in vitro bactericidal activity against both Gram-negative and Gram-positive pathogens, with generally low toxicity for human cells. Despite Gly being a more flexible residue, NMR structural studies showed little difference in structure and dynamics between the two peptides for the first 14 residues, with somewhat greater flexibility in the C-terminus of Kiadin resulting in a tighter structure of the peptide in the presence of sodium dodecyl sulfate micelles. AMPs found in organisms often exhibit minimal amino acid mutations, and such small differences in peptide conformation may be utilized to design more selective AMPs.

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Section: Kiadin and Dipgla-h Produced Similar CD Lineshapesupporting

confidence: 86%

Glycine Substitution Reduces Antimicrobial Activity and Helical Stretch of diPGLa-H in Lipid Micelles

et al. 2017

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“…A previous study has indicated that the antibacterial activities of fowlicidin-2 and tritrpticin were inhibited by the addition of salts and porcine serum [33]. In the present study, the hybrid peptides CA-FO and CA-TP were designed by combining CA (1)(2)(3)(4)(5)(6)(7)(8) with the most potent region of Fowlicidin-2 (1-15) [33] or the antimicrobial center of tritrpticin (7)(8)(9)(10)(11)(12)(13) [34,35]. We indicated the success of hybridization in designing AMPs with increased salt resistance and cell selectivity.…”

Section: Introductionmentioning

confidence: 90%

“…2 Purity was determined by reverse-phase high performance liquid chromatography (RP-HPLC). 3 Grand average of hydropathicity (GRAVY). Higher positive score indicates greater hydrophobicity and vice versa.…”

Section: Physicochemical Parameters Of Peptidesmentioning

confidence: 99%

“…During the past few years, intensive researches have invested into identification of novel antibiotics. Antimicrobial peptides (AMPs) have rapidly attracted attention as potential candidate for developing novel therapeutic agents [3,4]. AMPs that serve as the chemical barrier of the innate immune system in various organisms [5,6] are broad-spectrum endogenous antibiotics effective against a broad range of invading pathogens, including Gram-positive and negative bacteria, fungi as well as viruses [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Hybridization with Insect Cecropin A (1–8) Improve the Stability and Selectivity of Naturally Occurring Peptides

Yang

Wang

et al. 2020

IJMS

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Antimicrobial peptides (AMPs) offer great hope and a promising opportunity to overcome the rapid development of drug-resistant pathogenic microbes. However, AMPs often lack the stability required for a successful systemic drug. Hybridizing different AMPs is a simple and effective strategy to obtain novel peptides. N-terminal fragment of cecropin A (CA (1-8)) is often used to hybridize with other AMPs to reduce cytotoxicity. However, hybridizing with CA (1-8) in improving the stability of AMPs is not clear. Therefore, a series of peptides were designed by combining with CA (1–8) and their antibacterial activity and stability in the presence of salts and human serum were evaluated. The resultant α-helical hybrid peptide CA-FO composed of CA (1-8) and the most potent region of Fowlicidin-2 (FO (1–15)) exhibited excellent antibacterial activity (2-8 μM) and cell selectivity toward bacterial over mammalian cells. Moreover, CA-FO still retained vigorous antimicrobial activity in the presence of human serum and salts at physiological concentrations. CA-FO exhibited effective antibacterial activity by increasing membrane permeability and damaging membrane integrity. In conclusion, these results indicated the success of hybridization in designing and optimizing AMPs with improved stability and selectivity and the peptide CA-FO can be further evaluated as peptide-therapy to treat bacterial infections.

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“…Maravic and co-workers studied the effect of conformational flexibility in antimicrobial activity upon modification of a natural poorly active antimicrobial peptides PGLaÀ H. [25] They designed and synthesized a bunch of small cationic (charges varies from + 4 to + 7) peptides and conducted the antibacterial activity studies of the same with various Gram-positive and Gramnegative bacterial pathogens including the ESCAPE pathogens such as E. coli, K. pneumoniae, P. aeruginosa, A. baumannii and S. aureus. [26] Among the various number of Gly residue rich peptides (named as Kiadin), Kiadin-2 (KIAKGALKALKIAKVALKAL-NH 2 ) was found to be the most potent against Gram-negative pathogens.…”

Section: Conformational Effect On Natural Ampsmentioning

confidence: 99%

Cationic Amphiphilic Peptides: Synthetic Antimicrobial Agents Inspired by Nature

Kundu

2020

ChemMedChem

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Antimicrobial peptides are ubiquitous in multicellular organisms and have served as defense mechanisms for their successful evolution and throughout their life cycle. These peptides are short cationic amphiphilic polypeptides of fewer than 50 amino acids containing either a few disulfide-linked cysteine residues with a characteristic β-sheet-rich structure or linear α-helical conformations with hydrophilic side chains at one side of the helix and hydrophobic side chains on the other side. Antimicrobial peptides cause bacterial cell lysis either by direct cellsurface damage via electrostatic interactions between the cationic side chains of the peptide and the negatively charged cell surface, or by indirect modulation of the host defense systems. Electrostatic interactions lead to bacterial cell membrane disruption followed by leakage of cellular components and finally bacterial cell death. Because of their unusual mechanism of cell damage, antimicrobial peptides are effective against drug-resistant bacteria and may therefore prove more effective than classical antibiotics in certain cases. Currently, around 3000 natural antimicrobial peptides from six kingdoms (bacteria, archaea, protists, fungi, plants, and animals) have been isolated and sequenced. However, only a few of them are under clinical trials and/or in the commercial development stage for the treatment of bacterial infections caused by antibiotic-resistant bacteria. Moreover, high structural complexity, poor pharmacokinetic properties, and low antibacterial activity of natural antimicrobial peptides hinder their progress in drug development. To overcome these hurdles, researchers have become increasingly interested in modification and nature-inspired synthetic antimicrobial peptides. This review discusses some of the recent studies reported on antimicrobial peptides.

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PGLa-H tandem-repeat peptides active against multidrug resistant clinical bacterial isolates

Cited by 23 publications

References 63 publications

Glycine Substitution Reduces Antimicrobial Activity and Helical Stretch of diPGLa-H in Lipid Micelles

Glycine Substitution Reduces Antimicrobial Activity and Helical Stretch of diPGLa-H in Lipid Micelles

Hybridization with Insect Cecropin A (1–8) Improve the Stability and Selectivity of Naturally Occurring Peptides

Cationic Amphiphilic Peptides: Synthetic Antimicrobial Agents Inspired by Nature

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