Alessandro Lovari
A novel dendrimeric peptide with antimicrobial properties: structure-function analysis of SB056
SCORCIAPINO, MARIANO ANDREA;VARGIU, ATTILIO VITTORIO;RUGGERONE, PAOLO;CASU, MARIANO;RINALDI, ANDREA
2012-01-01
Abstract
The novel antimicrobial peptide with a dimeric dendrimer scaffold, SB056, was empirically optimized by highthroughput screening. This procedure produced an intriguing primary sequence whose structure-function analysis is described here. The alternating pattern of hydrophilic and hydrophobic amino acids suggests the possibility that SB056 is a membraneactive peptide that forms amphiphilic b-strands in a lipid environment. Circular dichroism confirmed that the cationic SB056 folds as b-sheets in the presence of anionic vesicles. Lipid monolayer surface pressure experiments revealed unusual kinetics of monolayer penetration, which suggest lipid-induced aggregation as a membranolytic mechanism. NMR analyses of the linear monomer and the dendrimeric SB056 in water and in 30% trifluoroethanol, on the other hand, yielded essentially unstructured conformations, supporting the excellent solubility and storage properties of this compound. However, simulated annealing showed that many residues lie in the b-region of the Ramachandran plot, and molecular-dynamics simulations confirmed the propensity of this peptide to fold as a b-type conformation. The excellent solubility in water and the lipid-induced oligomerization characteristics of this peptide thus shed light on its mechanism of antimicrobial action, which may also be relevant for systems that can form toxic b-amyloid fibrils when in contact with cellular membranes. Functionally, SB056 showed high activity against Gram-negative bacteria and some limited activity against Gram-positive bacteria. Its potency against Gram-negative strains was comparable (on a molar basis) to that of colistin and polymyxin B, with an even broader spectrum of activity than numerous other reference compounds.File | Size | Format | |
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Biophys_J 2012.pdf Solo gestori archivio
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Scorciapino et al_Biophys J 2012_SM.pdf Solo gestori archivio
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1.97 MB | Adobe PDF | & nbsp; View / Open Request a copy |
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