engleski

Predicting the therapeutic index of peptide antibiotics

Huge increase of antibiotical usage in the average human lifespan, the ever-increasing prevalence of antibiotic resistance and almost empty antibiotic pipelines of the pharmaceutical industry, created a great need for new antibiotics. Antimicrobial peptides (AMP) are evolutionary ancient weapons.Every single multicellular organism examined up to day posses AMPs which they use to fend off bacteria. AMPs target “ microbial Achilles heel” , a design features of microbial membranes that are specific for prokaryotic cells.To design novel AMP antibiotics we must learn to appreciate the design principles that natural AMPs can teach us. In this work we use sequence attributes such as peptide preference to enter membrane, its maximal hydrophobic moment and amino acid frequencies to estimate peptide therapeutic index. The present work is only the first step in attempts to discover sequence features which can distinguish peptide antibiotics from peptide toxins. Even so, it opens doors to proteome scanning or to peptide design with a goal to find novel peptide antibiotics different from all known antibiotics.

peptide antibiotics; peptide toxins; therapeutic index

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