Topoisomeric Membrane-Active Peptides: A Review of the Last Two Decades

Abstract

In recent decades, bioactive peptides have been gaining recognition in various biomedical areas, such as intracellular drug delivery (cell-penetrating peptides, CPPs) or anti-infective action (antimicrobial peptides, AMPs), closely associated to their distinct mode of interaction with biological membranes. Exploiting the interaction of membrane-active peptides with diverse targets (healthy, tumoral, bacterial or parasitic cell membranes) is opening encouraging prospects for peptides in therapeutics. However, ordinary peptides formed by L-amino acids are easily decomposed by proteases in biological fluids. One way to sidestep this limitation is to use topoisomers, namely versions of the peptide made up of D-amino acids in either canonic (enantio) or inverted (retroenantio) sequence. Rearranging peptide sequences in this fashion provides a certain degree of native structure mimicry that, in appropriate contexts, may deliver desirable biological activity while avoiding protease degradation. In this review, we will focus on recent accounts of membrane-active topoisomeric peptides with therapeutic applications as CPP drug delivery vectors, or as antimicrobial and anticancer candidates. We will also discuss the most common modes of interaction of these peptides with their membrane targets.

Triazole-Bridged Peptides with Enhanced Antimicrobial Activity and Potency against Pathogenic Bacteria

“…During recent years, AMPs were elaborated as anticancer peptides (ACPs) in various types of cancer . ACPs act by similar processes against cancer cells and most often disturb the structure of the phospholipid bilayer and form pores leading to cell lysis …”

“…35 ACPs act by similar processes against cancer cells and most often disturb the structure of the phospholipid bilayer and form pores leading to cell lysis. 36 In previous studies, we have already observed such effects for several sC18 variants 15,20 and, thus, elucidated the activity of the triazole-bridged peptides when in contact with cancerous HeLa cells. After incubating the cells for 24 h with various peptide concentrations, we found the highest toxicity for peptides 8A and 8B, demonstrating again their increased activity compared to the linear RL-8.…”