SPECIFIC ANTIMICROBIAL AND HEMOLYTIC ACTIVITIES OF 18-RESIDUE PEPTIDES DERIVED FROM THE AMINO-TERMINAL REGION OF THE TOXIN PARDAXIN

Peptides are part of the host defense system against bacteria and fung i in species right across the evolutionary scale. However, endogenous antibacterial peptides are often composed of 25 residues or more and, therefore, are not ideal for therapeutic use. Hence it is of considera ble interest to design and engineer short peptides having antimicrobia l activity, Peptides composed of 18 amino acids, derived from the N-te rminal region of the 33-residue toxin pardaxin (PX), GFFALIPKIISSPLFKT LLSAVGSALSSSGEQE, were synthesized and examined for biological activit ies, Peptide corresponding to the 1-18 stretch of PX exhibited antimic robial activity only against Escherichia coli and not against Gram-pos itive microorganisms. The peptide also did not possess hemolytic activ ity. Replacement of P7 by A resulted in a peptide possessing both anti bacterial and hemolytic activity. Substitution of both K residues by Q in the 'A' analog resulted in a peptide having only hemolytic activit y. Conformational analysis of these peptides and investigation of thei r model membrane permeabilizing activities indicated that selective ac tivity can be explained by their biophysical properties. Hence, by a r ational design approach based on biophysical principles, it should be possible to generate short peptides having specific biological activit y.