Naslov
Sinteza i konformacijska analiza desmuramil di-, tri- i tetrapeptida
(Synthesis and conformational study of desmuramyl di-, tri- and tetrapeptides)

Autori
Paurević, Marija ; Ribić, Rosana ; Kodrin, Ivan ; Biljan, Ivana ; Tomić, Srđanka

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

Izvornik
25. Hrvatski skup kemičara i kemijskih inženjera s međunarodnim sudjelovanjem : knjiga sažetaka / Đaković, Marijana ; Miljanić, Snežana ; Šantić, Ana ; Vianello, Robert - Zagreb : Hrvatsko kemijsko društvo, 2017, 146-146

ISBN
978-953-55232-7-7

Skup
25. Hrvatski skup kemičara i kemijskih inženjera s međunarodnim sudjelovanjem

Mjesto i datum
Poreč, Hrvatska, 19.04.2017. - 22.04.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
desmuramilpeptidi ; konformacijska analiza ; adjuvanti
(desmuramyl peptides ; conformational study ; adjuvants)

Sažetak
Muramyldipeptide (MDP), N-acetylmuramyl-L- alanyl-D-isoglutamine, is the smallest structural unit of peptidoglycans displaying immunostimulating (adjuvant) activity. Structure-activity relationship studies of muropeptides suggest that the desmuramyl dipeptide part (L-Ala-D-isoGln) is responsible for the adjuvant activity [1]. Primary structure modifications as well as their conformational changes may be responsible for changes in biological activity of peptides. Increase of lipophilicity in the N- and C- terminus of the dipeptide, such as introduced adamantly group at the N- terminal amino acid, can significantly improve pharmacological properties of desmuramyl peptides. Synthesis as well as conformational computational and experimental NMR analysis of corresponding desmuramyl dipeptide, tripeptide and tetrapeptide derivatives in zwitterionic and non-zwitterionic form was performed. L-Alanyl-D-isoglutamine was obtained by the removal of N- and C- protecting groups from commercially available dipeptide. Tri- and tetrapeptides were obtained by consecutive attachment of corresponding amino acids (1-adamantyl-glycine and serine) to desmuramyl dipeptide, using optimized coupling methodology (EDC/HOBt coupling reagents in the mixture of solvents CH2Cl2/1, 4- dioxane 1:1). (S)-1- adamantyl-glycyl-L-alanyl-D-isoglutamine was prepared in four synthetic steps using more efficient method than previously reported [2, 3]. The most stable conformers of synthesized peptides were determined. A systematic conformational space search was performed by means of molecular and quantum mechanical study in solution, which was modelled as a polarizable continuum. Hydrogen bonds were determined by using the QTAIM population analysis method. Calculated conformers were compared with those obtained in solution by NMR study in deuterated water and DMSO.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

Napomena
We wish to thank the Croatian Science Foundation for support (project IP-2014-09-7899).

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