Journal of Biomolecular Research & Therapeutics

Abstract

Conformational Studies of [¹¹Ψ¹²(CN₄)]ScyII and [¹⁵Ψ¹⁶(CN₄)]ScyII– Two Scyliorhinin II Analogues by means of 2D NMR Spectroscopy and Theoretical Methods

Krzysztof Brzozowski, Emilia Sikorska, Hanna Miecznikowska, Katarzyna Konecko, Rafał Ślusarz, Jolanta Kumirska, Witold Mozga,Jacek Olczak, Janusz Zabrocki, Sylwia Rodziewicz-Motowidło and Zbigniew Kaczyński

A conformational analysis of two analogues of scyliorhinin II [11?12(CN4])]ScyII and [15?16(CN4)]ScyII was performed in DMSO-d6. 2D NMR techniques and restrained molecular dynamics were applied. Our previous studies had shown Scyliorhinin II adopts three cis peptide bonds in DMSO-d6 solution. Moreover, in its two analogues [Aib16] ScyII and [Sar16]ScyII, we also found cis peptide bond geometries. Taking above into consideration, we decided to perform extensive conformational studies of restrained ScyII analogues. To do so, we introduced tetrazole groups into either of peptides studied. These peptides were synthesized by the solid-phase method using the Fmoc chemistry. In the case of two analogues, the following spectra were recorded: TOCSY, NOESY, ROESY, DQF-COSY and set of temperature ones. To obtain final structures, we performed restrained molecular dynamics simulations carried out using CHARMM force field as implemented in XPLOR 3.11 programm. Our calculations resulted in two ensembles of 10 conformations each. Comparing the obtained structures, we found that introduction of a 1,5-substituted tetrazole ring influences the three dimensional structure both locally and globally.