engleski

Sequence attributes for estimating the therapeutic index of peptide antibiotics

The therapeutic index (TI) of peptide antibiotics is defined as the ratio of hemolytic to antimicrobial activity. We constructed the database of 51 non-homologous helical antimicrobial peptides, isolated from frogs, with associated therapeutic index values determined on E. coli and human erythrocytes. Sequence attributes calculated by the SPLIT 3.5 server (split.pmfst.hr/split) are used for developing relationships between peptide structure and its therapeutic index. Helical amphipathic segments and G, Q, H, D, E amino acid frequencies are positively correlated with TI. High preferences for transmembrane helix conformation are negatively correlated with TI. The composite predictor is developed as a specific combination of these sequence-based parameters. Corresponding log-log model for estimating the therapeutic index exhibits good correlation (r = 0.9) with experimental TI values.

peptide antibiotics; therapeutic index; amphipathicity; amino acid frequencies; membrane helix preferences; structure-activity relationships

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