GENERATION OF ANALOGS HAVING POTENT ANTIMICROBIAL AND HEMOLYTIC ACTIVITIES WITH MINIMAL CHANGES FROM AN INACTIVE 16-RESIDUE PEPTIDE CORRESPONDING TO THE HELICAL REGION OF STAPHYLOCOCCUS-AUREUS DELTA-TOXIN
Vm. Dhople et R. Nagaraj, GENERATION OF ANALOGS HAVING POTENT ANTIMICROBIAL AND HEMOLYTIC ACTIVITIES WITH MINIMAL CHANGES FROM AN INACTIVE 16-RESIDUE PEPTIDE CORRESPONDING TO THE HELICAL REGION OF STAPHYLOCOCCUS-AUREUS DELTA-TOXIN, Protein engineering, 8(3), 1995, pp. 315-318
The delta-toxin is a 26-residue peptide from Staphylococcus aureus wit
h the sequence formyl-MAQDIISTIGDLVKWIIDTVNKFTKK. NMR studies indicate
that the segment IISTIGDLVKWIIDTV occurs in an alpha-helical conforma
tion in the toxin, A synthetic peptide corresponding to this segment,
although helical, did not exhibit hemolytic activity. Since charged re
sidues like D and K are likely to modulate cytolytic activity, analogs
of the 16-residue peptide were synthesized where D was systematically
replaced by K, Analogs in which the first D and both Ds were replaced
by K showed potent antimicrobial and hemolytic activities. The analog
in which the second D was replaced by K was relatively less active, H
owever, all the peptides showed an a-helical structure with similar he
lical content. The activities of the peptides were found to correlate
directly with their ability to permeabilize model membranes. Thus, by
minimal judicious replacement of charged amino acids, it should be pos
sible to generate cytolytic peptides from short segments of peptide to
xins.