Dataset Information

Role of Amphiphilicity in the Design of Synthetic Mimics of Antimicrobial Peptides with Gram-negative Activity.

ABSTRACT: Two new series of aryl SMAMPs (synthetic mimics of antimicrobial peptides) with facially amphiphilic (FA) and disrupted amphiphilic (DA) topologies were designed and synthesized to directly assess the role of amphiphilicity on their antimicrobial activity against gram-positive and gram-negative bacteria in closely related structures. The FA SMAMPs displayed broad spectrum antimicrobial activity against both gram-positive S. aureus and gram-negative E. coli, whereas the DA SMAMPs, which contained a polar amide bond in between the hydrophobic moieties, only exhibited activity towards S. aureus with increasing hydrophobicity. The integy moment (IW) was used to quantify the amphiphilicity of the SMAMPs and confirmed that it is critical for the design of SMAMPs with gram-negative activity.

SUBMITTER: Thaker HD

PROVIDER: S-EPMC3694626 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of Amphiphilicity in the Design of Synthetic Mimics of Antimicrobial Peptides with Gram-negative Activity.

Thaker Hitesh D HD Cankaya Alper A Scott Richard W RW Tew Gregory N GN

ACS medicinal chemistry letters 20130501 5

Two new series of aryl SMAMPs (synthetic mimics of antimicrobial peptides) with facially amphiphilic (FA) and disrupted amphiphilic (DA) topologies were designed and synthesized to directly assess the role of amphiphilicity on their antimicrobial activity against gram-positive and gram-negative bacteria in closely related structures. The FA SMAMPs displayed broad spectrum antimicrobial activity against both gram-positive <i>S. aureus</i> and gram-negative <i>E. coli</i>, whereas the DA SMAMPs, w ...[more]

PMID: 23814644

Similar Datasets

Project description:Antimicrobial peptides (AMPs) are ubiquitous amongst living organisms and are part of the innate immune system with the ability to kill pathogens directly or indirectly by modulating the immune system. AMPs have potential as a novel therapeutic against bacteria due to their quick-acting mechanism of action that prevents bacteria from developing resistance. Additionally, there is a dire need for therapeutics with activity specifically against Gram-negative bacterial infections that are intrinsically difficult to treat, with or without acquired drug resistance. Development of new antibiotics has slowed in recent years and novel therapeutics (like AMPs) with a focus against Gram-negative bacteria are needed. We designed eight novel AMPs, termed PHNX peptides, using ab initio computational design (database filtering technology combined with the novel positional analysis on APD3 dataset of AMPs with activity against Gram-negative bacteria) and assessed their theoretical function using published machine learning algorithms, and finally, validated their activity in our laboratory. These AMPs were tested to establish their minimum inhibitory concentration (MIC) and half-maximal effective concentration (EC50) under CLSI methodology against antibiotic resistant and antibiotic susceptible Escherichia coli and Staphylococcus aureus. Laboratory-based experimental results were compared to computationally predicted activities for each of the peptides to ascertain the accuracy of the computational tools used. PHNX-1 demonstrated antibacterial activity (under high and low-salt conditions) against antibiotic resistant and susceptible strains of Gram-positive and Gram-negative bacteria and PHNX-4 to -8 demonstrated low-salt antibacterial activity only. The AMPs were then evaluated for cytotoxicity using hemolysis against human red blood cells and demonstrated some hemolysis which needs to be further evaluated. In this study, we successfully developed a design methodology to create synthetic AMPs with a narrow spectrum of activity where the PHNX AMPs demonstrated higher antibacterial activity against Gram-negative bacteria compared to Gram-positive bacteria. Thus, these peptides present novel synthetic peptides with a potential for therapeutic use. Based on our findings, we propose upfront selection of the peptide dataset for analysis, an additional step of positional analysis to add to the ab initio database filtering technology (DFT) method, and we present laboratory data on the novel, synthetically designed AMPs to validate the results of the computational approach. We aim to conduct future in vivo studies which could establish these AMPs for clinical use.

Dataset Information

Role of Amphiphilicity in the Design of Synthetic Mimics of Antimicrobial Peptides with Gram-negative Activity.

Publications

Role of Amphiphilicity in the Design of Synthetic Mimics of Antimicrobial Peptides with Gram-negative Activity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets