Highly Efficient Cu(I)-Catalyzed Synthesis of N-Heterocycles through a Cyclization-Triggered Addition of Alkynes

摘要

The characterization of conformational dynamics observed innnon-native states of proteins is of particular importance to furthernour understanding of protein folding and misfolding. As a class ofnnon-native protein states, intrinsically unstructured proteins (IUPs)nhave gained particular interest lately due to their important role innprotein folding diseases.n1nNMR spectroscopy is the technique ofnchoice to investigate the dynamic ensemble of conformational statesncharacterizing non-native states of proteins. Previous NMR spec-ntroscopic investigations based on J-coupling analysis as well asnRDC measurement have revealed significant differences in aminonacid specific sampling of φ,ψ space, but little is known aboutnconformational preferences characterizing the side-chain angle u00021.nHowever, from the analysis of several homo- and heteronuclearn3nJ-couplings the distribution of the u00021 side-chain torsion angle cannbe determined.n2nOf the six possible couplings defining u00021, then3nJ(H ,Hu0003)-coupling constant is the best parametrized and has beennmeasured for small unstructured peptides,n3nbut not for largernpolypeptide chains due to the limited spectral resolution.