Membrane‐Active Small Molecules: Designs Inspired by Antimicrobial Peptides

Abstract

Infectious diseases continue to be one of the major contributors to human morbidity. The rapid rate at which pathogenic microorganisms have developed resistance against frontline antimicrobials has compelled scientists to look for new alternatives. Given their vast antimicrobial repertoire, substantial research effort has been dedicated toward the development of antimicrobial peptides (AMPs) as alternative drugs. However, inherent limitations of AMPs have driven substantial efforts worldwide to develop synthetic mimics of AMPs. This review focuses on the progress that has been made toward the development of small molecules that emulate the properties of AMPs, both in terms of design and biological activity. Herein we provide an extensive discussion of the structural features of various designs and we examine biological properties that have been exploited. Furthermore, we raise a number of questions for which the field has yet to provide solutions and discuss possible future research directions that remain either unexploited or underexploited.

Anticandidal activity of synthetic peptides: Mechanism of action revealed by scanning electron and fluorescence microscopies and synergism effect with nystatin

“…To assess the pore formation induced by peptides, the method described by Oliveira et al 12 was employed, using propidium iodide (PI) uptake. The C. albicans cells were grown and treated as mentioned above.…”

“…To face this global health challenge, synthetic antimicrobial peptides (SAMPs) have emerged as new drugs or even as adjuvants to commercial drugs 11,12 because the development of new technologies has allowed the reduction of costs for synthesis and achieving high purity, as well as making it possible to obtain SAMPs with specific modifications, such as cyclization, alanine scanning, or amino acid substitution 11–13 . Generally, SAMPs are positively charged and have amphipathic properties, enabling them to interact with cell membranes, inducing pore formation 13 …”

Mode of Action of a Designed Antimicrobial Peptide: High Potency against Cryptococcus neoformans

“…A number of these naturally occurring molecules are endowed with antimicrobial activities; however, their use is restricted to topical applications owing to their cytotoxicity (19). Extensive research in this field has led to the development of synthetically designed AMPs and peptidomimetics having in vitro antimicrobial activity and reduced cytotoxicity making them suitable candidates for antimicrobial drug design (20)(21)(22). Synthetically designed peptides have opened up immense opportunities in the field of drug design allowing modification to obtain optimal potency and selectivity.…”

Second Harmonic Generation Spectroscopy of Membrane Probe Dynamics in Gram-Positive Bacteria

“…The vast majority of antibacterial drugs are small molecules (1). In order to understand the reasons behind their successes and failures, it is necessary to first understand their initial interaction with bacterial cells, and more specifically, the bacterial membrane which is responsible for regulating small molecule uptake.…”