Pegylation and formulation strategy of Anti-Microbial Peptide (AMP) according to the quality by design approach

Manteghi, Reihaneh; Pallagi, Edina; Olajos, Gábor; Csóka, Ildikó

doi:10.1016/j.ejps.2019.105197

Cited by 26 publications

(33 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is generally known that the modification of PEG can improve the stability of peptides due to the entanglement of peptides by polymer chains. PEGylation has been widely applied in the structural optimization of AMPs 34–37 . However, the conjunction of PEG barely contributes to the improvement of the antimicrobial activity of peptides.…”

Section: Resultsmentioning

confidence: 99%

The effect of structural modification of antimicrobial peptides on their antimicrobial activity, hemolytic activity, and plasma stability

Wang¹,

Zou²,

Na³

et al. 2021

Journal of Peptide Science

View full text Add to dashboard Cite

In this article, a series of modifications were made on an antimicrobial peptide F2,5,12W, including altering the amino acid sequence, introducing cysteine and other typical amino acids, developing peptide dimers via disulfide bonds, and conjugating with mPEG, in order to enhance the antimicrobial activity, plasma stability, and reduce the hemolytic activity of peptides. The results showed that mPEG conjugation could significantly improve the plasma stability and reduce the hemolytic activity of peptides, while the antimicrobial activity decreased meanwhile. However, altering the sequence of the peptide without changing its amino acid composition had little impact on its antimicrobial activity and plasma stability. The introduction of cysteine enhanced the plasma stability of peptides conspicuously, but at the same time, the increased hydrophobicity of peptides increased their hemolysis. The antimicrobial mechanism and cytotoxicity of the peptides with relatively high antimicrobial activity were also studied. In general, this study provided some ideas for the rational design and structure optimization of antimicrobial peptides.

show abstract

Section: Resultsmentioning

confidence: 99%

The effect of structural modification of antimicrobial peptides on their antimicrobial activity, hemolytic activity, and plasma stability

Wang¹,

Zou²,

Na³

et al. 2021

Journal of Peptide Science

View full text Add to dashboard Cite

show abstract

“…The parent compound (i.e., 1; Table 1; reported previously [18]) constitutes the basis for a comparative estimation of the effect of sPEG incorporation. Most examples of PEGylated AMPs reported in the literature contain much longer PEG chains at the termini [19][20][21][22][23][24][25][26][27][28][29][30][31][32], and therefore four oligomers with sPEG moieties at either the N-terminus (Table 1: subgroup I, i.e., 2 and 3) or at both termini (subgroup II, i.e., 4 and 5) were included in the present set of analogues. Additionally, to study the effect of both the positioning of the sPEG spacer units in the oligomer sequence and the number of sPEG moieties introduced, we included subgroup designs in which the parent 12-mer was separated into either two or three fragments of six or four residues, respectively.…”

Section: Selection and Synthesis Of Peptidomimeticsmentioning

confidence: 99%

“…Modification of AMPs with polyethylene glycol (PEG) moieties at the N-terminus has been used as a strategy to overcome the challenge of low in vivo stability of AMPs [19,20]. The molecular weights (MWs) of PEG chains introduced to improve the bioavailability of AMPs and other biopharmaceuticals are typically high (i.e., 5-40 kDa [21]).…”

Section: Introductionmentioning

confidence: 99%

“…The molecular weights (MWs) of PEG chains introduced to improve the bioavailability of AMPs and other biopharmaceuticals are typically high (i.e., 5-40 kDa [21]). While the extensive PEG chains effectively shield the AMP sterically from proteolytic degradation, they may also restrict the accessibility of its bioactive domain(s), thereby diminishing its biological activity [19,21]. Low-MW PEG chains (i.e., MW in the range 2-5 kDa) have similarly been applied, but even these may confer reduced potency [19].…”

Section: Introductionmentioning

confidence: 99%

“…While the extensive PEG chains effectively shield the AMP sterically from proteolytic degradation, they may also restrict the accessibility of its bioactive domain(s), thereby diminishing its biological activity [19,21]. Low-MW PEG chains (i.e., MW in the range 2-5 kDa) have similarly been applied, but even these may confer reduced potency [19]. Thus, two previous studies by Imura et al showed that attachment of a 5 kDa PEG moiety at the N-terminus of tachyplesin I and magainin 2 resulted in conjugates with lowered cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties

Frederiksen

Louka

Mudaliar

et al. 2021

IJMS

View full text Add to dashboard Cite

PEGylation of antimicrobial peptides as a shielding tool that increases stability toward proteolytic degradation typically leads to concomitant loss of activity, whereas incorporation of ultrashort PEG-like amino acids (sPEGs) remains essentially unexplored. Here, modification of a peptide/β-peptoid hybrid with sPEGs was examined with respect to influence on hydrophobicity, antibacterial activity and effect on viability of mammalian cells for a set of 18 oligomers. Intriguingly, the degree of sPEG modification did not significantly affect hydrophobicity as measured by retention in reverse-phase HPLC. Antibacterial activity against both wild-type and drug-resistant strains of Escherichia coli and Acinetobacter baumannii (both Gram-negative pathogens) was retained or slightly improved (MICs in the range 2–16 µg/mL equal to 0.7–5.2 µM). All compounds in the series exhibited less than 10% hemolysis at 400 µg/mL. While the number of sPEG moieties appeared not to be clearly correlated with hemolytic activity, a trend toward slightly increased hemolytic activity was observed for analogues displaying the longest sPEGs. In contrast, within a subseries the viability of HepG2 liver cells was least affected by analogues displaying the longer sPEGs (with IC50 values of ~1280 µg/mL) as compared to most other analogues and the parent peptidomimetic (IC50 values in the range 330–800 µg/mL).

show abstract

Artificial peptides to induce membrane denaturation and disruption and modulate membrane composition and fusion

Lāce

Cotroneo

Hesselbarth

et al. 2022

Journal of Peptide Science

View full text Add to dashboard Cite

Membranes consisting of phospholipid bilayers are an essential constituent of eukaryotic cells and their compartments. The alteration of their composition, structure, and morphology plays an important role in modulating physiological processes, such as transport of molecules, cell migration, or signaling, but it can also lead to lethal effects. The three main classes of membrane‐active peptides that are responsible for inducing such alterations are cell‐penetrating peptides (CPPs), antimicrobial peptides (AMPs), and fusion peptides (FPs). These peptides are able to interact with lipid bilayers in highly specific and tightly regulated manners. They can either penetrate the membrane, inducing nondestructive, transient alterations, or disrupt, permeabilize, or translocate through it, or induce membrane fusion by generating attractive forces between two bilayers. Because of these properties, membrane‐active peptides have attracted the attention of the pharmaceutical industry, and naturally occurring bioactive structures have been used as a platform for synthetic modification and the development of artificial analogs with optimized therapeutic properties to transport biologically active cargos or serve as novel antimicrobial agents. In this review, we focus on synthetic membrane interacting peptides with bioactivity comparable with their natural counterparts and describe their mechanism of action.

show abstract

Pegylation and formulation strategy of Anti-Microbial Peptide (AMP) according to the quality by design approach

Cited by 26 publications

References 36 publications

The effect of structural modification of antimicrobial peptides on their antimicrobial activity, hemolytic activity, and plasma stability

The effect of structural modification of antimicrobial peptides on their antimicrobial activity, hemolytic activity, and plasma stability

Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties

Artificial peptides to induce membrane denaturation and disruption and modulate membrane composition and fusion

Contact Info

Product

Resources

About