Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals?

Abstract

The concept of antimicrobial peptides (AMPs) as potent pharmaceuticals is firmly established in the literature, and most research articles on this topic conclude by stating that AMPs represent promising therapeutic agents against bacterial and fungal agents. Indeed, early research in this field showed that AMPs were diverse in nature, had high activities with low minimal inhibitory concentrations, had broad spectrums of activity against bacterial, fungal and viral pathogens, and could easily be manipulated to alter their specificities, reduce their cytotoxicities and increase their antimicrobial activities. Unfortunately, commercial development of these peptides, for even the simplest of applications, has been very limited. With some peptides there are obstacles with their manufacture, in vivo efficacy and in vivo retention. More recently, the focus has shifted. Contemporary research now uses a more sophisticated approach to develop AMPs that surmount many of these prior obstacles. AMP mimetics, hybrid AMPs, AMP congeners, cyclotides and stabilised AMPs, AMP conjugates and immobilised AMPs have all emerged with selective or ‘targeted’ antimicrobial activities, improved retention, or unique abilities that allow them to bind to medical or industrial surfaces. These groups of new peptides have creative medical and industrial application potentials to treat antibiotic-resistant bacterial infections and septic shock, to preserve food or to sanitise surfaces both in vitro and in vivo.

Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

“…But the expression of atpD , a gene encoding α subunit of F 1 F 0 -ATPase [41], was upregulated although not statistically significant. Considering that AMPs GH12 function via the mechanism of accumulating at the bacterial membrane and inserting into lipid bilayers [21,42,43], we speculate that GH12 may directly affect the activity of F 1 F 0 -ATPase, which is located at cell membrane as well. Previous studies implied that the ATPase activity does not necessarily correlate with transcription or translation levels of associated genes [44].…”

Actualidades en terapéutica: nuevos antibacterianos

“…Los PAM tienen la ventaja de que se encuentran ampliamente distribuidos en la naturaleza, en los reinos Protista, Monera, Fungi, Plantae y Animalia [91].…”

“…Empero, el desarrollo farmacéutico de estas sustancias no ha sido tan exitoso, debido a inconvenientes en cuanto a sus características químicas y farmacocinéticas, además de dudas acerca de su seguridad y el alto costo de producción [91,92].…”

Three-dimensional NMR Structure of Hen Egg Gallin (Chicken Ovodefensin) Reveals a New Variation of the β-Defensin Fold

“…A highly promising approach to overcome this issue is to explore and exploit the huge diversity of innovative bioactive-engineered molecules provided by nature to fight off microbes. Among these natural products involved in the defense systems of living organisms, antimicrobial peptides, also called host defense peptides, may represent new clues to investigate (5)(6)(7)(8)(9)(10). These natural molecules of innate immunity ensure the defense of a multitude of organisms (plants, insects, and vertebrates) against the majority of pathogenic organisms.…”

“…The consensus sequence X n CX 4 -6 CX 3-4 CX 9 CX [5][6] CCX n corresponds to that of mammal ␤-defensins. The determination of the first tridi-mensional NMR structures of king penguin AvBD103b and chicken AvBD2 defensins showed the disulfide bridge motif typical of ␤-defensins (i.e.…”