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 PKLLKTFLSKWIG (SPFK), a 13-residue peptide with antimicrobial and hemolytic activities, have been investigated. Retro peptides with C-terminal acid and amide exhibited antibacterial activities comparable with those of SPFK. Their hemolytic activities were, however, only marginally lower. The diastereo analog with C-terminal acid was not antibacterial and was weakly hemolytic. Amidation of this analog could restore antibacterial activity. Both retro analogs were unordered in aqueous medium but had a propensity for a helical structure 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 biological activity such as hemolytic activity. Also, introduction of enantiomeric amino acids in a short peptide to generate a diastereomer may result in loss of structure as well as antimicrobial and hemolytic activities, unless compensated by an increase in positive charges.
Subbalakshmi
C
C
Centre for Cellular and Molecular Biology, Hyderabad, India.
Nagaraj
R
R
Sitaram
N
N
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002147:Calmodulin / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000378:metabolism; D006461:Hemolysis; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014270:Trifluoroethanol / Q000737:chemistry
D000900:Anti-Bacterial Agents; D002147:Calmodulin; D010455:Peptides; D014270:Trifluoroethanol