Antimicrobial Dendrimeric Peptides: Structure, Activity and New Therapeutic Applications

Abstract

Microbial resistance to conventional antibiotics is one of the most outstanding medical and scientific challenges of our times. Despite the recognised need for new anti-infective agents, however, very few new drugs have been brought to the market and to the clinic in the last three decades. This review highlights the properties of a new class of antibiotics, namely dendrimeric peptides. These intriguing novel compounds, generally made of multiple peptidic sequences linked to an inner branched core, display an array of antibacterial, antiviral and antifungal activities, usually coupled to low haemolytic activity. In addition, several peptides synthesized in oligobranched form proved to be promising tools for the selective treatment of cancer cells.

Dendrimers as Pharmaceutical Excipients: Synthesis, Properties, Toxicity and Biomedical Applications

“…Consequently, they became an important tool in the treatment of viral infections, especially in human Dendrimers' classifications according to their roles in the formulation. The constitution of the dendrimer may confer different activities, namely, anti-inflammatory activity, antiviral activity and antimicrobial activity [13,15]. As a pharmaceutical excipient, dendrimers may enhance distinct properties of the formulation according to the phase of drug product development [27].…”

Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity

“…The number of bacterial pathogens resistant to available classes of antibiotics is increasing, with the UK government estimating 10 million deaths due to antimicrobial resistance (AMR) by 2050 if no countermeasures are taken (1,2). As a global threat, the World Health Organization recognised in 2015 that discovery of new antibiotic classes is an essential element of a global action plan to tackle AMR (3).…”

Function Oriented Molecular Design: Dendrimers as Novel Antimicrobials

“…Multiple dipeptides composed of tryptophan and arginine residues were coupled on dendrimers synthetized by Kallenbach et al The chemical characteristic mediated by arginine residues, positively charged, confers the possibility to mediate electrostatic interactions with the cell wall. The tryptophan residues with the lipophilic parts are able to interact with membranes compromising their integrity [ 144 , 145 ]. In this scenario a very interesting dendrimer modified with peptides was obtained with the G3KL dendrimer against P. aeruginosa and Acinetobacter baumannii .…”

“…In this scenario a very interesting dendrimer modified with peptides was obtained with the G3KL dendrimer against P. aeruginosa and Acinetobacter baumannii . The peptido-dendrimer structure contained dipeptides (lysine and leucine), coupled via lysine residues and proved to be active also against carbapenemase producer clinical strains [ 145 , 146 ]. Peptido-dendrimers based on di-, tetra-, or octavalent lysine cores bound with tetra-(RLYR) or octapeptides (RLYRKVYG) exhibited a strong antibacterial activity against both Gram-positives and Gram-negatives, but a major increase of the activity was observed against Gram-negative bacteria.…”

“…Glycoproteins gp120 and gp141 are supposed to interact with these dendrimers preventing viral entry [ 144 ]. The same dendrimers have been, successively, proven to be potent, specific, and selective inhibitors of the replication of the unrelated enterovirus A71, but their mechanism remains unclear [ 145 ]. The work and structure-activity relationship studies were extended to determine the basic traits that could be responsible for the important and dual (against HIV and enteroviruses) antiviral activity previously shown.…”