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April 3, 2026Artificial Cells Nanomedicine and BiotechnologyOpen Access

Lipidation of a nuclear localization sequence enhances broad-spectrum antimicrobial activity: synthesis, characterization, and in silico analysis

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Authors

RMRani MaharaniPadjadjaran UniversityTFTaufik Muhammad FakihBandung Islamic UniversityMMMuhamad Imam MuhajirPadjadjaran University

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Implication

Evaluates lipidation effects on antimicrobial activity in a cationic peptide, suggesting a potential strategy for broad-spectrum agents.

Key Points

  • The aim is to determine whether lipidation of the PKKKRKV peptide can improve its antimicrobial properties and explore the resulting structure-activity relationships.
  • Synthesis of five PKKKRKV-based lipopeptides using Fmoc solid-phase peptide synthesis.
  • Conjugation of lipopeptides with various fatty acids (C16-C18).
  • Purification of compounds by RP-HPLC and characterization via mass spectrometry and NMR.
  • Assessment of antimicrobial activity against various bacteria and fungi using broth microdilution assays.
  • Conduct of in silico studies including molecular docking and dynamics simulations.
  • Lipidation significantly enhanced antimicrobial activity of the peptides.
  • LP-5 (C18:1, unsaturated) showed the broadest spectrum with MIC values of 11.59-23.19 µM against Gram-positive and Gram-negative bacteria.
  • LP-2 (C16:0, saturated) was selectively potent against E. coli with an MIC of 6.96 µM.
  • LP-4 and LP-5 exhibited small HOMO-LUMO gaps (∼0.111-0.112 eV), indicating higher electronic reactivity.

Cite This Study

Maharani et al. (2026) studied this question.

synapsesocial.com/papers/69cf5dd55a333a821460bd10https://doi.org/10.1080/21691401.2026.2649071
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