Fig 2 -

(a) Per-residue RMSFs for ZnF1 in Model 1 to Model 4. (b) The three-dimensional structure diagram of ZnF1 (4OPX). The interaction interface of ZnF1/DSB and ZnF1/CAT are represented by blue and red, respectively, and the corresponding residues are shown in blue and red. (c) Per-residue energy contribution spectra of ZnF1 on the surface of ZnF1/DSB for Model 1 to Model 4. Red, blue, green, and yellow bars represent Lig1, Lig2, Lig3, and without ligand binding to CAT (marked as WLig). (d) Per-residue energy contribution spectra of ZnF1 on the surface of ZnF1/CAT for Model 1 to Model 4. Red, blue, green, and yellow bars represent Lig1, Lig2, Lig3, and WLig.</p

The calculated (MM/GBSA) binding free energies of ZnF1/CAT.

The calculated (MM/GBSA) binding free energies of ZnF1/CAT.</p

The calculated (MMGBSA) binding free energies of the ZnF1/DSB for Model 1 to Model 4.

The calculated (MMGBSA) binding free energies of the ZnF1/DSB for Model 1 to Model 4.</p

The calculated (MMGBSA) binding free energies of ZnF3/CAT.

The calculated (MMGBSA) binding free energies of ZnF3/CAT.</p

Fig 3 -

(a) Per-residue RMSFs for ZnF 3 in Model 1 to Model 4. (b) The three-dimensional structure diagram of ZnF3 (4OPX). The interaction interfaces of ZnF3/DSB and ZnF3/CAT are represented by blue and red, respectively, and the corresponding residues are shown in blue and red. (c) Per-residue energy contribution spectra of ZnF3 on the surface of ZnF3/DSB. Red, blue, green, and yellow bars represent Lig1, Lig2, Lig3, and WLig. (d) Per-residue energy contribution spectra of ZnF3 on the surface of ZnF3/CAT. Red, blue, green, and yellow bars represent Lig1, Lig2, Lig3, and WLig.</p

Fig 4 -

(a) Comparation of per-residue RMSFs between DSB/ZnF1/ZnF3/CAT and DSB/ZnF1/ZnF3/CAT/Lig1. (b) Comparation of per-residue RMSFs between DSB/ZnF1/ZnF3/CAT and DSB/ZnF1/ZnF3/CAT/Lig2. (c) Comparation of per-residue RMSFs between DSB/ZnF1/ZnF3/CAT and DSB/ZnF1/ZnF3/CAT/Lig3. (d) Three-dimensional structure diagram of CAT (4OPX). Interaction interfaces of CAT/DSB (residue 40 to 90), CAT/ZnF1 (residue 30 to 70), CAT/ZnF3 (residue 30 to 46 and residue 200 to 205) and catalytic site (residue 330 to 380) are represented by red, blue, yellow and green, respectively. (e) Per-residue energy contribution spectra of CAT on the surface of CAT/DSB. (f) Per-residue energy contribution spectra of CAT on the surface of CAT/ZnF1. (g-h) Per-residue energy contribution spectra of CAT on the surface of CAT/ZnF3. Finally, the color bars in (e-h) are the same, with red, blue, green, and yellow bars representing Lig1, Lig2, Lig3, and WLig (without ligand) binding to CAT, respectively. All current serial number of residues plus 530 are serial number of residues of CAT in 4OPX.</p

Fig 1 -

(a) Three-dimensional diagram of the binding system (4OPX). ZnF1, ZnF3 and CAT (including WGR) are depicted in red, yellow, and green, respectively. DSB is depicted in blue. Ligand is shown in purple stick model. (b) Two-dimensional diagram of C10H10FNO2, marked as Lig1. (c) Two-dimensional diagram of C16H11NO5, marked as Lig2. (c) Two-dimensional diagram of C22H22N2O5, marked as Lig3.</p

Construction of Isocytosine Scaffolds via DNA-Compatible Biginelli-like Reaction

Herein we report a DNA-compatible Biginelli reaction to construct isocytosine scaffolds. This reaction utilizes a one-pot reaction of DNA-conjugated guanidines with aldehydes and methyl cyanoacetates to give isocytosine derivatives, and the method is well compatible with different types of substrates. This is the first report on the synthesis of an isocytosine backbone in the field of DNA-compatible organic synthesis. The successful development of this reaction can widen the chemical space of DELs

Schematic diagram of binding mechanisms among ligands, CAT, ZnF1, ZnF3 and DSB (4OPX).

CAT area includes WGR (green cartoon), HD (red cartoon) and ART (blue cartoon). (a) Interaction between ligand and CAT. (b) Interaction between ZnF1 and CAT. (c) Interaction between ZnF3 and CAT. (d) Interaction between DSB and CAT. (e) Interaction between ZnF1 and DSB. (f) Interaction between ZnF3 and DSB. (g) Interaction between ZnF1 and ZnF3.</p

The calculated (MMGBSA) binding free energies of ZnF3/DSB.

The calculated (MMGBSA) binding free energies of ZnF3/DSB.</p