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Review
. 2014 Aug 30:7:229-37.
doi: 10.2147/IDR.S49229. eCollection 2014.

Peptidomimetics as a new generation of antimicrobial agents: current progress

Patricia Méndez-Samperio  1
Affiliations
Review

Peptidomimetics as a new generation of antimicrobial agents: current progress

Patricia Méndez-Samperio. Infect Drug Resist. .

Abstract

Antibiotic resistance is an increasing public health concern around the world. Rapid increase in the emergence of multidrug-resistant bacteria has been the target of extensive research efforts to develop a novel class of antibiotics. Antimicrobial peptides (AMPs) are small cationic amphiphilic peptides, which play an important role in the defense against bacterial infections through disruption of their membranes. They have been regarded as a potential source of future antibiotics, owing to a remarkable set of advantageous properties such as broad-spectrum activity, and they do not readily induce drug-resistance. However, AMPs have some intrinsic drawbacks, such as susceptibility to enzymatic degradation, toxicity, and high production cost. Currently, a new class of AMPs termed "peptidomimetics" have been developed, which can mimic the bactericidal mechanism of AMPs, while being stable to enzymatic degradation and displaying potent activity against multidrug-resistant bacteria. This review will focus on current findings of antimicrobial peptidomimetics. The potential future directions in the development of more potent analogs of peptidomimetics as a new generation of antimicrobial agents are also presented.

Keywords: antimicrobial peptides; drug resistance; infection.

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Figures

Figure 1
Figure 1
Three-dimensional structures of human antimicrobial peptides. Notes: The Protein Data Bank identification for these structures are 3GNY for dimeric crystal structure of human α-defensin 1 (or human neutrophil peptide-1); 1E4S for human beta defensin 1; and 2K6O for human cathelicidin LL-37 in complex with sodium dodecyl sulfate micelles. Structural coordinates were obtained from the Research Collaboratory for Structural Bioinformatics Protein Databank (http://www.rcsb.org). The significance of ‘1’ and ‘2’is for dimeric crystal structure of human α-defensin 1 (two peptides: ‘1’ and ‘2’, together).
Figure 2
Figure 2
Representative structures of α-AA and γ-AApeptides.
Figure 3
Figure 3
General building block strategy for the synthesis of AApeptides. Notes: Each coupling cycle includes an Fmoc deprotection using 20% piperidine in DMF and coupling of α-AA or γ-AApeptides building blocks onto resin in the presence of DIC/ODhbt in DMF. After desired sequences are assembled, they are cleaved. Abbreviations: DIC, diisopropylcarbodiimide; DMF, dimethyl fluoride; Fmoc, 9- fluorenylmethyloxycarbonyl; ODhbt, 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine; γ-AA, γ-AApeptides; α-AA, α-AApeptides.
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