Naslov
Structure characterisation of bioactive compounds and their interactions

Autori
Jednačak, Tomislav

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

Izvornik
Adriatic NMR conference 2020 : Book of abstracts / Bregović, Nikola ; Namjesnik, Danijel ; Novak, Predrag ; Parlov Vuković, Jelena - Zagreb, 2020, 15-15

ISBN
978-953-6076-58-1

Skup
4th Adriatic NMR conference 2020

Mjesto i datum
Peroj, Hrvatska; Vodnjan, Hrvatska, 22.09.2020. - 24.09.2020

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
biomolecular interactions ; structure characterisation ; NMR spectroscopy ; ligands ; macromolecular receptors ; synthesis

Sažetak
Biomolecular interactions play essential roles in all cellular processes, such as protein synthesis, gene regulation, molecular organisation and recognition events. Determining the three- dimensional structure of ligands, their receptors and complexes is crucial for understanding molecular mechanisms and dynamics involved in these interactions. The first step to achieve this goal is the synthesis of small molecules, which can act as ligands for biomolecular receptors and thus regulate their function. In order to obtain bioactive ligands with the desired physico- chemical properties and to optimize product yields, the syntheses can be monitored in real time by employing in-line techniques. Further analysis of complex reaction mixtures is carried out on-line using a hyphenated system which combines HPLC and SPE with cryo-NMR detection (HPLC-SPE/cryo-NMR). This methodology is applied to monitor the reaction progress, explain the side-reaction mechanisms and unambiguously characterize the reaction components. In the next stage, binding of the prepared ligands to their biological targets is studied by a combined use of cryo-electron microscopy, X-ray diffraction and NMR techniques based on saturation transfer difference (STD), paramagnetic relaxation enhancements (PREs), transferred nuclear Overhauser effect (trNOESY), translational diffusion (DOSY) and chemical shift perturbations (CSP). The results obtained for free and bound ligands can provide valuable data on the groups responsible for binding, ligand conformation, orientation, immersion depth, binding modes and epitopes. Structural information is further complemented with biochemical assays and molecular dynamics simulations to assess the structure- activity relationships and design the compounds with enhanced biological properties.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA