Design and Application of Antimicrobial Peptide Conjugates

Abstract

Antimicrobial peptides (AMPs) are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT) or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry.

Drug delivery systems designed to overcome antimicrobial resistance

“…Over the past years, many research teams have worked on the pharmacomodulation of AMPs or on developing a number of AMP‐antibiotic combinations or conjugates. These efforts have enhanced ATB efficacy, reduced the toxicity of both components, improved the permeability and broadened the ATB spectrum of conventional antibiotics . With regard to the Trojan horse strategy, we will focus on the conjugation of ATBs with AMPs, the latter serving as delivery vehicules for the former.…”

“…With regard to the Trojan horse strategy, we will focus on the conjugation of ATBs with AMPs, the latter serving as delivery vehicules for the former. Other potential applications of AMPs in anti‐infectious treatment have already been studied in previous reviews …”

“…In structural analysis, AMPs possess different secondary structures, often stabilized by disulfide bridges . They can be divided into four subgroups: α‐helical AMPs (eg, magainin and cathelicidin [LL‐37]), β‐sheet AMPs (eg, defensin, protegrin, tachyplesin, arenicin, extended AMPs (eg, indolicidin and bactenecin) (Figure ) . However, there are also other ways to classify AMPs as found in the AMP Databases …”

“…Interestingly, they do not interact with any specific target sites . Consequently, pathogens have developed a resistance to AMPs relatively slowly, and few such cases of pathogenic resistance have been reported thus far . As an example, tyrothricin has been in clinical use for over 60 years with no major pathogenic resistance described .…”

“…As an example, tyrothricin has been in clinical use for over 60 years with no major pathogenic resistance described . Besides their ATB potential, AMPs have recently been used as antibiotic‐carriers in Trojan horse strategies . AMP‐antibiotic conjugates have exhibited enhanced ATB activity, particularly against MDR Gram‐negative pathogens …”