Antimicrobial peptide mimics for improved therapeutic properties

Abstract

The relatively recent recognition of the major role played by antimicrobial peptides (AMPs) in sustaining an effective host response to immune challenges was greatly influenced by studies of amphibian peptides. AMPs are also widely regarded as a potential source of future antibiotics owing to a remarkable set of advantageous properties ranging from molecular simplicity to low-resistance swift-kill of a broad range of microbial cells. However, the peptide formula per se, represents less than ideal drug candidates, namely because of poor bioavailability issues, potential immunogenicity, optional toxicity and high production costs. To address these issues, synthetic peptides have been designed, reproducing the critical peptide biophysical characteristic in unnatural sequence-specific oligomers. Thus, the use of peptidomimetics to overcome the limitations inherent to peptides physical characteristics is becoming an important and promising approach for improving the therapeutic potential of AMPs. Here, we review most recent advances in the design strategies and the biophysical properties of the main classes of mimics to natural AMPs, emphasizing the importance of structure-activity relationship studies in fine-tuning of their physicochemical attributes for improved antimicrobial properties.

Insect proteins as a potential source of antimicrobial peptides in livestock production. A review

“…An important resistance mechanism for certain classes of antimicrobials is reduced drug accumulation due to limited uptake, mainly referring to Gram-negative bacteria, or enhanced efflux mainly referring to Gram-positive bacteria (Andersson et al, 2016;Joo et al, 2016). Another mechanism is phenotypic resistance (Grampositive and Gram-negative bacteria) based on specific growth patterns such as biofilm formation (Rotem and Mor, 2009;Li et al, 2012;Andersson et al, 2016;Joo et al, 2016). However, the main problem is multidrug resistance which is costly and has generated significant problems in veterinary medicine and animal production.…”

Human Defensins: Potential Tools for Clinical Applications

“…To overcome this problem, diastereomers of antimicrobial peptides with D-configured amino acids were synthesized and successfully applied by topical and subcutaneous treatment [94,95]. Hence, many efforts have recently been made to focus on the pharmaceutical administration and modification of antimicrobial peptides as new leads for clinical therapeutic applications [96][97][98][99][100][101].…”

A Comparative Study of Antimicrobial Profile Having Broad Spectrum Bacteriocins Against Antibiotics

“…De novo peptide design approaches have also been used for various purposes such as structurebased modeling, predictive algorithms, and introduction of non-coded modifications to conventional peptide chemistry [39].…”