Photosensitizer-peptoid conjugates for photoinactivation of Gram-negative bacteria: structure-activity relationship and mechanistic studies.

Multitarget engagement is considered an effective strategy to overcome the threat of bacterial infection, and antimicrobials with multiple mechanisms of action have been successful as natural chemical weaponry. Here, we synthesized a library of photosensitizer-peptoid conjugates (PsPCs) as novel antimicrobial photodynamic therapy (aPDT) agents. The peptoids, linkers, and photosensitizers were varied, and their structure-antimicrobial activity relationships against Escherichia coli were evaluated; PsPC 9 was indicated to be the most promising photoresponsive antimicrobial agent among the synthesized PsPCs.

Helicity Modulation Improves the Selectivity of Antimicrobial Peptoids.

The modulation of conformational flexibility in antimicrobial peptides (AMPs) has been investigated as a strategy to improve their efficacy against bacterial pathogens while reducing their toxicity. Here, we synthesized a library of helicity-modulated antimicrobial peptoids by the position-specific incorporation of helix-inducing monomers. The peptoids displayed minimal variations in hydrophobicity, which permitted the specific assessment of the effect of conformational differences on antimicrobial activity and selectivity.