Evaluation of Anti‐Chlamydial Effect of a Synthetic Linear Peptide

Abstract

AbstractInspired by the broad spectrum of antimicrobial activity exhibited by Magainins and SMAP‐28, and based on their chemical structures, several linear peptides were designed and synthesized with the aim of achieving peptides possessing promising anti‐chlamydial activity with lower cytotoxicity towards human normal cell lines. We found these peptides to be cytotoxic against human normal cell lines, except for one designated as DJ‐7, which was utilized in subsequent experiments, while the others were excluded. Peptide DJ‐7 was readily synthesized using standard Fmoc‐SPPS, and its anti‐chlamydial activity was investigated against HeLa cells (ATCC CCL‐2) infected with Chlamydia trachomatis L2 (ATCC VR‐902B) at MOI 1 for 2 hours, followed by treatment with increasing concentrations of peptide DJ‐7 (15–60 μg/mL). Microscopic examination revealed a significant reduction in the total number of bacterial inclusions in cells by around 50 % and 80 % after treatment with 15 μg/mL (5.5 μM) and 30 μg/mL (11 μM) of peptide DJ‐7, respectively, compared to control untreated infected cells. The impact of peptide DJ‐7 treatment on the development of infectious C. trachomatis serovar L2 progeny was investigated, demonstrating a significant decrease in infectious chlamydia after treatment with peptide DJ‐7. This suggests that chlamydia failed to complete its typical developmental cycle, indicating that peptide DJ‐7 exhibits anti‐chlamydial properties, by disrupting the normal bacterial development process. Our results indicate that peptide DJ‐7 is a promising lead peptide for further development as a potential anti‐chlamydial agent.