Current synthetic chemistry towards cyclic antimicrobial peptides

Abstract

Antimicrobial peptides (AMPs) have great potentials for developing novel antibiotics against multi‐drug resistant (MDR) bacteria. However, the clinical application of AMPs is limited due to their poor protease stability and high hemolytic toxicity. Various strategies have been widely explored to improve the pharmacological properties of natural or artificial antimicrobial peptides, including D‐ or non‐natural amino acid residue replacement, backbone modification, cyclization, PEGlytion, and lipidation. Among others, peptide cyclization, which has been widely applied to enhance the biostability and target selectivity of bioactive peptide, is a very appealing and promising strategy for developing novel antibiotics based on AMPs. Herein, we summarize the current strategies for synthesizing cyclic antimicrobial peptides and the resulting influence of peptide cyclization on the biological activities.

Mixture-Based Screening of Focused Combinatorial Libraries by NMR: Application to the Antiapoptotic Protein hMcl-1

“…In our application, a validated (by means of NMR spectroscopy and ITC), low micromolar agent with reasonably low molecular weight and ample possibilities for optimizations was identified, representing in principle a novel chemotype targeting hMcl-1. The approach is relatively simple and could find general applicability in a variety of scenarios, including, for example, the creation of libraries of cyclic peptides, ,− or similar to the f HTS by NMR, for the optimization of an initial binding scaffold identified by other methods.…”

Novel self-assembling cyclic peptides with reversible supramolecular nanostructures

“…This model introduces a novel strategy to develop cyclic peptide-based self-assembly peptide systems that may serve as supramolecular materials for different applications as immunosuppressants, antibiotics, antivirals, or anticancer drugs. [57][58][59] However, its poor solubility in water prevented the formation of stand-alone hydrogels with mechanical properties suited for biotechnology applications, thus suggesting that some optimization still had to be done.…”

The dual antimicrobial and immunomodulatory roles of host defense peptides and their applications in animal production

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