In:
Biochemical Journal, Portland Press Ltd., Vol. 349, No. 3 ( 2000-08-01), p. 747-755
Abstract:
Analogues of a structurally equivalent version of the antimicrobial decameric cyclic peptide gramicidin S, GS10 [cyclo-(Val-Lys-Leu-D-Tyr-Pro)2], were designed to study the effect of distortion in the β-sheet/β-turn structure of the cyclic peptide on its biological activity. In one approach, the hydrophobic nature of GS10 was conserved, and single amino acids in its backbone were replaced systematically with their corresponding enantiomers to give five diastereoisomeric analogues. In a related approach, a more basic and hydrophilic analogue of GS10 [cyclo-(Lys-Val-Lys-D-Tyr-Pro5-Lys-Leu-Lys-D-Tyr-Pro10)] , together with two of its monosubstituted diastereoisomeric analogues (featuring D-Lys1 or D-Val2 respectively), were synthesized. CD spectra were measured in a variety of environments, i.e. aqueous, aqueous trifluoroethanol and those containing SDS micelles or phospholipid vesicles. In comparison with GS10 spectra, CD spectra of both groups of analogues in these environments exhibited structural distortion. Moreover, compared with GS10, antimicrobial and haemolytic activities of the analogues were drastically decreased, implying the existence of a threshold minimum amphipathicity for effective biological activity. However, in both groups of analogues, there was a correlation between amphipathicity and antimicrobial and haemolytic activities. In the second group of analogues, both electrostatic and hydrophobic factors were related to their antimicrobial and haemolytic activities. In order to gain an insight into the nature of the biological activity of the two classes of cyclic peptides, the relationship of their structure to interaction with lipid membranes, and the implied mechanisms, were analysed in some detail in the present study.
Type of Medium:
Online Resource
ISSN:
0264-6021
,
1470-8728
Language:
English
Publisher:
Portland Press Ltd.
Publication Date:
2000
detail.hit.zdb_id:
1473095-9
SSG:
12
