Fig. 1: Synthesis and applications of trifunctional sphingomyelin derivatives (TFSMs). | Nature Communications

Fig. 1: Synthesis and applications of trifunctional sphingomyelin derivatives (TFSMs).

From: Trifunctional sphingomyelin derivatives enable nanoscale resolution of sphingomyelin turnover in physiological and infection processes via expansion microscopy

Fig. 1: Synthesis and applications of trifunctional sphingomyelin derivatives (TFSMs).

a Trifunctional sphingomyelin derivative TFSM 1. The molecule can be coupled to different conjugation partners (e.g., biotin, fluorescent dyes, quencher molecules), offering a broad range of applications. Illustrated above, a FRET pair was coupled allowing to determine the cleavage status of the probe. The third functionality is the primary amino group for fixation in expansion microscopy, in this case, glutaraldehyde fixation. b Synthesis of trifunctional sphingomyelin derivatives TFSM 1 and TFSM 2. Synthetic route for TFSM 1: (i) MOM-Cl, DIPEA, DCM, 0 °C, 4 h, 85%; (ii) TBAF, THF, 0 °C, 2 h, 97%; (iii) β-bromoethylphosphoryl dichloride, pyridine, DCM, 0 °C, 4 h, 82%; (iv) N,N-dimethylpropargylamine, CHCl3, MeCN, iPrOH, rt → 45 °C, 2 d, 63%; v) 1. HCl, MeOH, rt, 2 h; 2. 13, DIPEA, DCM, rt, 18 h, 85% in two steps; vi) TFA, DCM, 0 °C, 2 h, quant. Synthetic route for TFSM 2: (i) MOM-Cl, DIPEA, DCM, 0 °C → rt, 4 h, 74%; (ii) TBAF, THF, 0 °C → rt, 1 h, 78%; (iii) β-bromoethylphosphoryl dichloride, pyridine, DCM, 0 °C, 5 h, 56%; (iv) N,N-dimethylpropargylamine, CHCl3, MeCN, iPrOH, rt, 6 d, 69%; (v) 1. HCl, MeOH, rt, 3.5 h; 2. 14, DIPEA, DCM, rt, 3 d, 85% in two steps; (vi) TFA, DCM, 0 °C, 2.5 h, quant. Figure 1a was created with BioRender.com, released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.

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