Design of Antimicrobially Active Small Amphiphilic Peptide Dendrimers

Abstract

Novel polyfunctional small amphiphilic peptide dendrimers characterized by incorporation of a new core compounds – tris-amino acids or tetrakis-amino alcohols that originated from a series of basic amino acids – were efficiently synthesized. These new core elements yielded molecules with multiple branching and (+5)/(+6) charge at the 1-st dendrimer generation. Dendrimers exhibited significant antimicrobial potency against Gram(+) and Gram(-) strains involving also multiresistant reference strains (S. aureus ATCC 43300 and E. coli ATCC BAA-198). In addition, high activity against fungi from the Candida genus was detected. More charged and more hydrophobic peptide dendrimers expressed hemolytic properties.

Peptide-Based Polymer Therapeutics

“…Zhu et al [162] has recently tested the antimicrobial activity of a set of branched His-Lys dendrimers on Candida species and other fungi, finding that the four-branched dendrimer H2K4b was the most active among all. There are many other dendrimers that have been tested to be effective against a variety of bacterial strains, including multidrug-resistant strains [157,[224][225][226][227].…”

Dendrimers—revolutionary drugs for infectious diseases

“…According to other data on this subject, these results imply that structural factors such as distribution of charged and lipophylic groups determine antimicrobial and hemolytic properties. Thus, proper manipulation with these parameters may lead to the production of dendrimers with optimal qualities—high biological activity and low cytoxicity 107…”

“…To challenge this problem many studies on potential antifungal dendrimers have been performed and yielded encouraging results. As in the case of bacteria, the mechanism of action underlying fungicidal properties of dendrimers is based on the interaction with the cell membrane which is followed by its disruption and cytoplasm leakage 107…”

Amino Acid‐Based Dendrimers

“…The results are consistent with the hypothesis that both activities result from some common properties of the histidine-rich dendrimer peptide -their endosomal-disrupting properties. A number of other dendrimer peptides have been reported to be effective against a variety of bacterial strains including multidrug-resistant strains [60][61][62][63][64]. It is generally observed that bacterial resistance to peptides or the dendrimers develops much less than to standard antibiotics such as vancomycin.…”