The antibacterial activity of peptide dendrimers and polymyxin B increases sharply above pH 7.4

Cai, Xingguang; Javor, Sacha; Gan, Bee‐Ha; Köhler, Thilo; Reymond, Jean‐Louis

doi:10.1039/d1cc01838h

Cited by 16 publications

(29 citation statements)

References 39 publications

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“…As such, pH modulation of AMPs can be considered as a strategy to combat common resistance mechanisms, and increase the potency of AMPs. 88,93,100 However, such a strategy might be carried out only in topical applications. 93…”

Section: Influence Of Ph On the Biological Activity Of Ampsmentioning

confidence: 99%

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

et al. 2021

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Section: Influence Of Ph On the Biological Activity Of Ampsmentioning

confidence: 99%

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

et al. 2021

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“…While AMPDs do not aggregate like the related transfection dendrimers described in the next section, we recently discovered that their antibacterial activity can be preserved at the acidic pH of 5.5 typical of biofilms and human skin by removing their eight low pK a amino termini. [43] In the same study, we discovered that AMPD activity strongly increases in slightly alkaline media corresponding to chronic wounds to include Klebsiella pneumoniae as well as methicillin resistant Staphylococcus aureus. We are currently fine-tuning the properties of our best AMPDs by altering their sequence and stereochemistry to improve their in vivo toxicity, half-life and antibacterial activity profile aiming for a clinical candidate.…”

Section: Discussionmentioning

confidence: 91%

Peptide Dendrimers: From Enzyme Models to Antimicrobials and Transfection Reagents

Reymond

2021

Chimia

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Aiming at studying cooperativity effects between amino acids in easily accessible protein models, we have explored the chemistry of peptide dendrimers, which we obtain as pure products by solid-phase peptide synthesis using a branching diamino acid such as lysine at every second or third position in a peptide sequence, followed by reverse-phase HPLC purification. This article reviews discoveries driven by combinatorial library synthesis and screening, including enantioselective esterase and aldolase enzyme models, cobalamin binding and peroxidase dendrimers, glycopeptide dendrimer biofilm inhibitors and their X-ray crystal structures as complexes with lectins, antimicrobial peptide dendrimers active against multidrug resistant Gram-negative bacteria, and transfection reagents for siRNA and CRISPR-Cas9 plasmid DNA. Latest developments include cheminformatics and artificial intelligence for exploring the peptide chemical space, and the principle of stereorandomization to understand the role of peptide chirality in activity.

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“…Environmental factors such as salt and PH levels affect the normal efficiency of AMPs. Recently, some techniques such as the modification of the amino acid sequences and PH modulation of peptides have been considered useful in order for AMPs to function normally in the presence of high-salt or high-PH environments [ 13 ].…”

Section: Structure and Properties Of Ampsmentioning

confidence: 99%

Detecting the Mechanism of Action of Antimicrobial Peptides by Using Microscopic Detection Techniques

Aslam

Firdos

et al. 2022

Foods

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Increasing antibiotic resistance has shifted researchers’ focus to antimicrobial peptides (AMPs) as alternatives to antibiotics. AMPs are small, positively charged, amphipathic peptides with secondary helical structures. They have the ability to disrupt the bacterial membrane and create wedges due to electrostatic differences. Water molecules enter the pathogens through those wedges and disrupt their normal cellular functioning, eventually causing the death of the pathogens. Keeping in mind the importance of AMPs, this review compiles recent data and is divided into three parts. The first part explains the AMP structure and properties, the second part comprises the spectroscopy techniques currently used for evaluating the AMP-bacterial targeting mechanism as well as its structure and safety; and the third part describes the production of AMPs from an animal source (whey protein). Most of the peptides that were used in recent studies have been either the precursors of a natural peptide or synthetic peptides with some modifications, but data on the exploitation of dairy protein are scarce. Among the little-studied milk proteins and peptides, in the last three years, whey protein has been studied the least based on the reported data. Because whey protein is a leftover part of cheese making that often drains out as cheese waste, causing soil and environmental pollution, today, the need of the hour is to produce safe AMPs from whey protein. The use of whey protein that is based on hydrolyzing lactic acid bacteria with some structural modifications can increase AMPs’ potency, stability, and safety, and it can also help to avoid soil and environmental pollution as a result of whey drainage.

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The antibacterial activity of peptide dendrimers and polymyxin B increases sharply above pH 7.4

Abstract: pH-activity profiling reveals that antimicrobial peptide dendrimers (AMPDs) kill Klebsiella pneumoniae and Methicillin-resistant Staphylococcus aureus (MRSA) at pH=8.0, against which they are inactive at pH=7.4, due to stronger electrostatic binding...

Cited by 16 publications

References 39 publications

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

Peptide Dendrimers: From Enzyme Models to Antimicrobials and Transfection Reagents

Detecting the Mechanism of Action of Antimicrobial Peptides by Using Microscopic Detection Techniques

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