CR22DK-S18G Breakthrough: Revealing a novel antimicrobial peptide with rifampicin and isoniazid-like potency against Mycobacterium tuberculosis - a comprehensive exploration from synthesis to immune modulation and selective action

Kaiser testResin Solid Phase Peptide Synthesis (SPSS)According to WHO, 1.6 million people died from Tuberculosis (TB) in 2021, making TB the secondleading infectious killer after COVID-19. 1,2,3In recent years, antimicrobial peptides (AMPs) with promising anti-TB activity have been identified.B1CTcu5 is a peptide amide, isolated in 2014 from the skin secretion of the Indian toad Clinotarsus curtipes, and showing initial MIC values of 12.5 g/mL against Mycobacterium tuberculosis (MTB). 4The objective of the present work was to generate a library of B1CTcu5 analogues by replacing Cys 15 and Cys 21 with Ala, Ser and/or Lys, and to evaluate their activity against MTB and cytotoxicity.Table 1.Cysteine replacement -Minimal inhibitory concentration of B1CTcu5 peptide analogs against Mycobacterium tuberculosis strains and cytotoxic activity on murine macrophages.Peptide analogs was evaluated at concentrations between 2 to 250 g/mL. Conclusions AcknowledgmentsIn conclusion, B1CTcu5 analogs show promise as a potential new peptide-based therapy against Mycobacterium tuberculosis, specially CRDK-s18G.