Investigation of the association and flexibility of cationic lipidic peptide dendrons by NMR spectroscopy.
The cationic peptide dendrons synthesized and studied are lower generation polylysine-based partial dendrimers with or without lipid chains in the core. The dendrons with lipidic chains can be utilized as protein and liposomal mimics because of their unique structural properties. The full assignments of three different dendrons (L)7(NH2)8, (C14)1(L)7(NH2)8 and (C14)3(L)7(NH2)8 were obtained in D2O and H2O/D2O using a 500 MHz NMR spectrometer. The hydrophobic lipidic core of branched polylysine dendrons was found to induce aggregation upon increasing concentration. Because non-lipidic dendrons do not self-assemble, the behaviour and internal structural features of two different dendrons with one and three C14 hydrocarbon chains were explored. The critical association concentration clearly depends on the number of core hydrophobic residues and the association starts at 0.025 mM for (C14)1(L)7(NH2)8 and 0.05 mM for (C14)3(L(7(NH2)8. Chemical shift analysis also revealed that the hydrophobic chains of the dendrons associate in the core, whereas the polar head groups (NH2) are mainly located at the surfaces of the aggregates. The T1 relaxation time measurements showed that the mobility of the hydrocarbon chain is greater with the monomeric form of dendron (C14)1(L)7(NH2)8) than that of monomer (C14)3(L)7(NH2)8. The inter-chain hydrophobic interactions restrict the flexibility of the dendron with three hydrocarbon chains. As expected, the flexibility of the monomeric form is higher than that of the aggregated state for both of the dendrons.
Zloh
Mire
M
Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK. mire.zloh@ulsop.ac.uk
Ramaswamy
Chandrasekaran
C
Sakthivel
Thiagarajan
T
Wilderspin
Andy
A
Florence
Alexander T
AT
D008074:Lipoproteins / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation
D008074:Lipoproteins; D010455:Peptides; D011107:Polylysine