Biological activities of retro and diastereo analogs of a 13-residue peptide with antimicrobial and hemolytic activities

The biological activities of synthetic retro and diastereo analogs of PKLLK TFLSKWIG (SPFK), a 13-residue peptide with antimicrobial and hemolytic acti vities, have been investigated. Retro peptides with C-terminal acid and ami de exhibited antibacterial activities comparable with those of SPFK. Their hemolytic activities were, however, only marginally lower. The diastereo an alog with C-terminal acid was not antibacterial and was weakly hemolytic. A midation of this analog could restore antibacterial activity. Both retro an alogs were unordered in aqueous medium but had a propensity for a helical s tructure in trifluoroethanol. However, diastereo analogs were unordered in both aqueous medium and trifluoroethanol. Thus, reversing the sequence in a short amphiphilic peptide may not always result in the selective loss of b iological activity such as hemolytic activity. Also, introduction of enanti omeric amino acids in a short peptide to generate a diastereomer may result in loss of structure as well as antimicrobial and hemolytic activities, un less compensated by an increase in positive charges.