CONFORMATION AND INTERACTIONS OF ALL-D-BOMBOLITIN-III, RETRO-ALL-D-BOMBOLITIN-III AND RETRO-BOMBOLITIN-III ANALOG IN AQUEOUS-SOLUTION AND IN THE PRESENCE OF DETERGENT MICELLES
A. Bisello et al., CONFORMATION AND INTERACTIONS OF ALL-D-BOMBOLITIN-III, RETRO-ALL-D-BOMBOLITIN-III AND RETRO-BOMBOLITIN-III ANALOG IN AQUEOUS-SOLUTION AND IN THE PRESENCE OF DETERGENT MICELLES, International journal of biological macromolecules, 17(5), 1995, pp. 273-282
Bombolitins are five structurally related heptadecapeptides which lyse
erythrocytes and liposomes and enhance the activity of phospholipase
A(2). The conformational properties of the all-D-, retro-all-D-, and r
etro-L-analogues of bombolitin III were investigated by circular dichr
oism (CD) and two-dimensional H-1-nuclear magnetic resonance (NMR) tec
hniques. In water, all three sequences are in a random conformation an
d aggregate to various extents depending on pH and concentration. The
two enantiomeric retro-sequences exhibit a higher propensity to form b
eta-aggregates, while the D-analogue of the native sequence fends to f
orm aggregates of alpha-helices. In the presence of an excess of sodiu
m dodecyl sulfate (SDS), the peptides fold into an amphiphilic alpha-h
elical conformation (left-handed in the case of the all-D sequences).
NMR studies on the L-retro-analogue indicate that the helical segment
is localized in the central part of the sequence. Combined CD and surf
ace tension measurements indicate that the critical micellar concentra
tion of SDS is raised in the presence of peptide and that helical fold
ing occurs before micelle formation. These results are interpreted in
terms of formation of peptide-detergent complexes. It is estimated tha
t the helical structure forms when 40-50 molecules of detergent are bo
und to each peptide molecule. These data and our previous results of i
n vitro biological tests confirm that the ability to form amphiphilic
helices is the major determinant of biological activity of bombolitins
.