Szintetikus és NMR kutatások peptidek és szénhidrátok körében = Synthetic and NMR studies of peptides and carbohydrates

Egy immunomodulans peptidoglikan-monomer (PGM) lipofil szarmazekainak konformaciojat 2D NMR es molekulamodellezes segitsegevel hataroztuk meg. A szubsztituensek okozta konformacio valtozasok a biologiai aktivitast nem befolyasoljak. Bakterialis endotoxinokat (LPS) gatlo LALF-14 hexadekapeptid LPS-kotődeset hasonlo modszerekkel vizsgalva kimutattuk, hogy a teljes LALF protein lipid-A-kotő ?-lemez regioja nem előfeltetele a LALF-14 - LPS-kotődesnek. Dodekapeptidekben NOE-meresekkel es molekulamodellezessel aromas gyűrű - amid-H kolcsonhatasokat mutattunk ki amelyek a helikalis terszerkezettel kapcsolatosak. Uj tipusu, haromkoteses glikozidos hidat tartalmazo glikomimetikumok első kepviselőikent glikozil-diszulfidokat es -szulfenamidokat szintetizaltunk. Hidrazino-pirimidinek es aromas aldehidek acilezesi reakcioban nukleozid-analog [1,2,4]triazolo[4,5-a]pirimidin-4-on szarmazekokat eredmenyeznek. Javaslatot tettunk ezen uj gyűrűzarasi reakcio mechanizmusara. Javasoltuk a Lipari-Szabo NMR relaxacios modszer kiterjeszteset. Modszerunkkel feherjekben meghatarozhato a kemiai eltolodasok anizotropiaja (CSA) es az un. geometriai faktor is. Uj TROSY modszert javasoltunk az NH-H? csatolasi allandok meresere feherjekben. Erzekeny, es pontos NMR modszereket fejlesztettunk ki gyengen orientalt kozegben maradek dipolaris csatolasok, es diasztereotop metilen-proton csatolasok dipolaris jarulekainak meresevel az uj glikomimetikumok terszerkezetenek jellemzesere. | 2D NMR and molecular modelling studies of lipophilic derivatives of peptidoglycan monomer (PGM) indicate that conformational changes induced by the substituents do not affect the biological activities of these compounds. Using similar approaches it was shown that binding of the LALF-14 inhibitor peptide to bacterial endotoxins (LPS) does not require the -sheet structure in the lipid-A binding region of full-size LALF protein as a prerequisite. Interactions between amide protons and side chain aromatic rings in helical dodecapeptides were identified by NOE-restrained molecular modelling. Diglycosyl disulfides and glycosyl sulfenamides were synthesized as the first representatives of novel glycomimetics with three-bond glycosidic linkages. Hydrazino-pyrimidines react with aromatic aldehydes under acylating conditions to furnish nucleoside analog [1,2,4]triazolo[4,5-a]pyrimidin-4-ones. A mechanism was proposed for these novel ring closing reactions. The Lipari-Szabo formalism for NMR relaxation data was extended for the determination of individual chemical shift anisotropies (CSA) and the geometry factors in proteins. A new TROSY sequence was developed to measure NH-H? couplings in proteins. Novel NMR methods were proposed to measure residual dipolar couplings and the dipolar contribution to the scalar coupling between diastereotopic protons in weakly aligned media. These NMR methods are of importance in the structural studies of the novel glycomimetics.