Abstract
A new method has been developed for the synthesis of spin-labeled thielocin B1 to allow for further structural validation of the interaction between thielocin B1 and proteasome-assembling chaperone 3 (PAC3). A spin-labeling reagent was introduced to the left-hand side of thielocin B1 and paramagnetic relaxation enhancement (PRE) experiments were conducted to determine its effects at the interface of PAC3 homodimer. Spin-labeling experiments were carried out in the presence of spin-labeled thielocin B1, and revealed a distinct decrease in the intensities of the NMR signals belonging to 16 of the amino acid residues of PAC3 homodimer. Furthermore, the results of additional in silico docking studies suggested that the left wing of thielocin B1 makes an initial interaction with the interface of PAC3 homodimer, and that the right wing of thielocin B1 then moves towards the β-sheet layers of PAC3 to induce the dissociation of PAC3 homodimer.
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Brown HC, Narasimhan S, Choi YM. J Org Chem. 1982;47:4702–8.
West CT, Donnelly SJ, Kooistra DA, Doyle MP. J Org Chem. 1973;38:2675–81.
Yao L, Smith BT, Aubé J. 1-azido-3-iodopropane was prepared by reported procedure. J Org Chem. 2004;69:1720–2.
Kappe CO. Angew Chem Int Ed. 2004;43:6250–84.
Parish RC, Stock LM. J Org Chem. 1965;30:927–9.
Song S, Zhao Y-M, Zhai H. Org Lett. 2011;13:6331–3.
Kunishima M, Kawachi C, Iwasaki F, Terao K, Tani S. Tetrahedron Lett. 1999;40:5327–30.
Kunishima M, Kawachi C, Hioki K, Terao K, Tani S. Tetrahedron. 2001;57:1551–8.
Staudinger H, Meyer J. Helv Chim Acta. 1919;2:635–46.
Burés J, Martin F, Urpi F, Vilarrasa J. J Org Chem. 2009;74:2203–6.
Tanaka T, Oikawa Y, Nakajima N, Hamada T, Yoshimitsu O. Chem Pharm Bull. 1987;35:2203–8.
Lovrić M, Cepanec I, Litvić M, Bartolinčić A, Vinković V. Croat Chem Acta. 2007;80:109–15.
Jung ME, Lyster MA. J Org Chem. 1977;42:3761–4.
Kamal A, Rao NV, Laxman E. Tetrahedron Lett. 1997;38:6945–8.
Olah JA, Narang SC, Gupta BGB, Malhotra R. Angew Chem Int Ed. 1979;18:612–4.
Sato T, Otera J, Nozaki H. J Org Chem. 1992;57:2166–9.
Tomizawa M. Ph.D. thesis, Tohoku University, Japan; 2009.
Bakunov S, Denicov AY, Tkachev AV. Tetrahedron. 1995;51:8565–72.
Yashiroda H, Mizushima T, Okamoto K, Kameyama T, Hayashi H, Kishimoto T, Niwa S, Kasahara M, Kurimoto E, Sakata E, Takagi K, Suzuki A, Hirano Y, Murata S, Kato K, Yamane T, Tanaka K. Nat Struct Mol Biol. 2008;15:228–36.
Molecular Operating Environment (MOE), ver. 2012. Chemical Computing Group Inc., Quebec; 2012.
Goddard TD, Kneller DG. SPARKY 3. University of California, San Francisco.
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Ohsawa, K. (2015). Synthesis of Spin-Labeled Thielocin B1 and Observation of Paramagnetic Relaxation Enhancement Effects. In: Total Synthesis of Thielocin B1 as a Protein-Protein Interaction Inhibitor of PAC3 Homodimer. Springer Theses. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55447-9_3
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DOI: https://doi.org/10.1007/978-4-431-55447-9_3
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