Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity

Daisuke Takahashi, Sanjeev K. Shukla, Om Prakash, Guolong Zhang

Research output: Contribution to journalReview articlepeer-review

254 Citations (Scopus)


Antimicrobial host defense peptides (HDPs) are a critical component of the innate immunity with microbicidal, endotoxin-neutralizing, and immunostimulatory properties. HDPs kill bacteria primarily through non-specific membrane lysis, therefore with a less likelihood of provoking resistance. Extensive structure-activity relationship studies with a number of HDPs have revealed that net charge, amphipathicity, hydrophobicity, and structural propensity are among the most important physicochemical and structural parameters that dictate their ability to interact with and disrupt membranes. A delicate balance among these factors, rather than a mere alteration of a single factor, is critically important for HDPs to ensure the antimicrobial potency and target cell selectivity. With a better understanding of the structural determinants of HDPs for their membrane-lytic activities, it is expected that novel HDP-based antimicrobials with minimum toxicity to eukaryotic cells can be developed for resistant infections, which have become a global public health crisis.

Original languageEnglish
Pages (from-to)1236-1241
Number of pages6
Issue number9
Publication statusPublished - Sept 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry


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