The collection includes files related to the publication: N. Skrzypczak, A. Buczkowski, W. Bohusz, E. Nowak, K. Tokarska, A. Leśniewska, A. M. Alzebari, P. Ruszkowski, M. Gdaniec, F. Bartl, P. Przybylski. Modifications of geldanamycin via CuAAC altering affinity to chaperone protein Hsp90 and cytotoxicity EuropeanJournalofMedicinalChemistry 256 (2023) 115450.
The collection is the Supplementary data to this article:
Supplementary data to this article contain: copies of all 1H and 13C NMR as well as FT-IR spectra for 1–37 together with selected 2D NMR correlations; x-ray data of 1 (Fig. S3), binding energy profits (ΔE; Table S1) and modes of GDM congeners 3, 4, 6, 7, 8, 10–12, 14, 16, 19, 20 and 23 with Hsp90 (Figs. S1–S3).
The collection includes figures used in the publication: :
Fig. 1 Geldanamycin (GDM) and its structural analogues (17-AAG and IPI-504) considered at various stages of clinical trials.
Fig. 2 The concept of designing a series of potentially active GDM derivatives.
Fig. 3 Structures of C(17)-alkyne and C(17)-azide geldanamycin derivatives (1 and 2) and their transformation into triazole congeners (3–37) via dipolar CuAAC cycloaddition.
Fig. 4 Structure of alkyne derivative 1 with the atom numbering, determined by x-ray crystallography (CCDC 2192495). Displacement ellipsoids are shown at the 50% probability level.
Fig. 5 1H–13C HMBC correlations illustrating successful formation of the triazole moiety and the linkage between (a) the triazole and benzoquinone portions, as well as between (b) the triazole and the C(17)-arm cap, for the case of derivative 23.
Fig. 6 Isothermal titration calorimetry (ITC) thermal effects of 30 μM Hsp90 solution titrated with 200 μM ligand solution of: geldanamycin GDM (grey circles ), 22 (blue squares ), 14 (red diamonds ) and 23 (green triangles ) in 10 mM phosphorous buffer solution (pH 7.4) at 25 ◦C. ITC curves of Hsp90 binding interactions with ligands were described with the one-site independent binding model (solid lines).
Fig. 7 Docking of GDM triazole congeners into the N-binding domain pocket of Hsp90 (PDB 3Q5J [38]): (a) 30, ΔE (30 – Hsp90) =- 51.12 kcal/mol; (b) 29, ΔE (29 – Hsp90) =- 54.83 kcal/mol; (c) 22, ΔE (22 – Hsp90) =- 44.18 kcal/mol; (d) 5, ΔE (5 – Hsp90) =- 45.81 kcal/mol; (e) 34, ΔE (34 – Hsp90) =- 44.39 kcal/mol; (f) 35, ΔE (35 – Hsp90) =- 33.18 kcal/mol; interactions between Hsp90 and GDM congeners are marked by yellow dots; calculated by MOG-PM6 using MYOZYME algorithm (Scigress F.J. 2.6, EU 3.1.9) [39].
The collection also included a file (References) with the list of literature used in this paper:
References - Literature cited in the publication