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Pregled bibliografske jedinice broj: 670693

Incorporation of peptidoglycan derivatives into lipid bilayers for the targeted delivery of immunomodulators characterised by NMR spectroscopy


Feher, Krisztina; Ribić, Rosana; Sinnaeve, Davy; Frkanec, Ruža; Martinis, C. Jose; Tomić, Srđanka; Szilagyi, Laszlo; Kover, E. Katalin
Incorporation of peptidoglycan derivatives into lipid bilayers for the targeted delivery of immunomodulators characterised by NMR spectroscopy // Abstract Book of the 2nd Meeting of Middle-European Societies for Immunology and Allergology / Polić, Bojan (ur.).
Rijeka: Zaklada Sveučilišta u Rijeci, 2013. str. 92-92 (poster, međunarodna recenzija, sažetak, znanstveni)


Naslov
Incorporation of peptidoglycan derivatives into lipid bilayers for the targeted delivery of immunomodulators characterised by NMR spectroscopy

Autori
Feher, Krisztina ; Ribić, Rosana ; Sinnaeve, Davy ; Frkanec, Ruža ; Martinis, C. Jose ; Tomić, Srđanka ; Szilagyi, Laszlo ; Kover, E. Katalin

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract Book of the 2nd Meeting of Middle-European Societies for Immunology and Allergology / Polić, Bojan - Rijeka : Zaklada Sveučilišta u Rijeci, 2013, 92-92

Skup
2nd Meeting of Middle-European Societies for Immunology and Allergology

Mjesto i datum
Opatija, Rijeka, 10-13.10.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Bacterial peptidoglycan; immunomodulators; lipid bilayers; NMR spectroscopy

Sažetak
Peptidoglycan (PGN) as well fragments and substances derived from it have well-documented immunomodulating properties exerted by potentiating host immune response. Such immunomodulators are urgently needed in many medical interventions, such as adjuvants in vaccines, in anti-inflammatory and anti-infective treatments well as in aiding cancer therapies. Targeted delivery of drugs to their site of action provides multiple advantages by increasing therapeutic efficiency and lowering the required dose while minimizing systemic toxicity. Phospholipid assemblies in particular are widely used as pharmaceutical carriers of drugs both by passive as well active targeting.We generated a molecular system aimed at the actively targeted delivery of PGN-based immunomodulators with the help of phospholipid assemblies. We have investigate the potential of using NMR spectroscopy as an efficient method of studying the encapsulation of targeting compounds into lipid bilayers and the interaction between them on a molecular level. We have utilised pulse-field gradient (PFG) NMR, nuclear Overhauser effect as well as Saturation Transfer Difference Spectroscopy. We investigated the interaction between the derivatives with the bicellar lipid assemblies made up of a long-chain and a short chain phosphatidylcholin. We have shown that the PGN derivatives are incorporated in the studied lipid bilayers by the change of the sign and intensity of the NOE in NOESY spectra as well as by the observation of slower translational diffusion in PFG NMR spectra. We determined the encapsulation efficiency under such conditions by utilising the equation driving the observed diffusion coefficients under fast exchange conditions. We have found more than 50% of the investigated compounds were entrapped in the lipid bilayers under the conditions used. We have utilised diffusion NMR of labile amide protons and STD experiments for the characterisation of the orientation of the studied derivatives in the bilayer. We have shown that the adamantyl group does penetrate the lipid core of the bilayer and acts as anchor of the PGN derivative cargo, while the hydrophilic mannose group is exposed on the surface and can act as a ligand targeting surface receptors, such as the macrophage mannose receptor in particular.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
021-0212432-2431 - Nove formulacije antigena i imunostimulatora - utjecaj na imunoreakciju (Ruža Frkanec, )
119-1191344-3121 - Sinteze i enzimske transformacije biološki aktivnih spojeva (Srđanka Tomić-Pisarović, )

Ustanove
Imunološki zavod d.d.,
Prirodoslovno-matematički fakultet, Zagreb