Dennison, Sarah R. and Phoenix, David A. (2011) Influence of C-Terminal Amidation on the Efficacy of Modelin-5. Biochemistry, 50 (9). pp. 1514-1523. ISSN 0006-2960
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Official URL: http://dx.doi.org/10.1021/bi101687t
To gain insight into the effects of amidation on the mechanism of membrane interaction, we studied two peptides modelin-5-COOH and modelin-5-CONH2 and found they exhibit high surface activities (23.2 and 27.1 mN/m, respectively). When they were tested against Escherichia coli, amidation was seen to increase efficacy approximately 10-fold. Our results demonstrated that both peptides adopted low levels of α-helix in solution (<20%); however, in the presence of E. coli lipid extract, modelin-5-CONH2 had a greater propensity (69%) than modelin-5-COOH (32%) to generate α-helical structure. The binding coefficient for both peptides was 10 μM, and the Hill coefficient approximated 1, suggesting that for both peptides the interactions with E. coli membranes were monomeric and comparable in strength. The peptides showed a clear preference for anionic lipid, with monolayer data showing that enhanced levels of helicity were associated with a greater pressure change (6 mN/m). Use of fluorescein-phosphatidylethanolamine showed the amidated version was able to generate greater levels of membrane disruption, which was confirmed by thermodynamic analysis. The data would imply that both peptides are able to initially bind to bilayer structures, but upon binding, the amidation stabilizes helix formation. This would be expected to help overcome a key rate-limiting step and generate higher local concentrations of peptide at the bilayer interface, which in turn would be predicted to increase efficacy.
|Subjects:||Medicine & dentistry > Medicine & dentistry not elsewhere classified|
|Schools:||Specialist Services > Directorate|
College of Science and Technology > School of Forensic and Applied Sciences
|Deposited By:||Jeannine Sullivan|
|Deposited On:||27 Mar 2012 10:56|
|Last Modified:||17 May 2016 12:29|
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