Protegrins are short (16-18 residues) cationic peptides
from porcine leukocytes that displaypotent, broad-spectrum antimicrobial activity. Protegrin-1 (PG-1), one o
f five natural homologues, adoptsa rigid
![](/images/gi<font color=)
fchars/beta2.gi
f" BORDER=0 ALIGN="middle">-hairpin structure that is stabilized by two disul
fide bonds. We have previously employed theprinciples o
f ![](/images/gi<font color=)
fchars/beta2.gi
f" BORDER=0 ALIGN="middle">-hairpin design to develop PG-1 variants that lack disul
fide bonds but nevertheless displaypotent antimicrobial activity [Lai, J. R., Huck, B. R., Weisblum, B., and Gellman, S. H. (2002)
Biochemistry41, 12835-12842.]. The activity o
f these disul
fide-
free variants, however, is attenuated in the presenceo
f salt, and the activity o
f PG-1 itsel
f is not. Salt-induced inactivation o
f host-de
fense peptides, such ashuman de
fensins, is thought to be important in some pathological situations (e.g., cystic
fibrosis), and thevariation in salt-sensitivity among our PG-1 analogues o
ffers a model system with which to explore theorigins o
f these salt e
ffects. We
find that the variations in antimicrobial activity among our peptides arecorrelated with the
folding propensities o
f these molecules and with the extent to which the peptidesinduce leakage o
f contents
from synthetic liposomes. Comparable correlations were observed between
folding and hemolytic activity. The extent to which added salt reduces antimicrobial activity parallels salte
ffects on vesicle perturbation, which suggests that the biological e
ffects o
f high salt concentrations arise
from modulation o
f peptide-membrane interactions.