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

Citation
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
Citations number
23
Categorie Soggetti
Biology
ISSN journal
01418130
Volume
17
Issue
5
Year of publication
1995
Pages
273 - 282
Database
ISI
SICI code
0141-8130(1995)17:5<273:CAIOAR>2.0.ZU;2-1
Abstract
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 .