Beilstein J. Org. Chem.2020,16, 2505–2522, doi:10.3762/bjoc.16.203
ligand-detected techniques.
1H,15N-HSQC and 1H,15N-TROSY-HSQC spectra
1H,15N-HSQCNMR spectra are a widely used tool to study the interaction of proteins with natural or synthetic ligands as well as other biomolecules [83]. This spectrum requires 15N-labeling of the protein of interest, which is easily
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Graphical Abstract
Figure 1:
Ligands targeting charged areas on protein surfaces discussed in this review. The protein shown as ...
Beilstein J. Org. Chem.2019,15, 513–520, doi:10.3762/bjoc.15.45
for p53-MDM2 inhibition by fluorescence polarization and 1H,15NHSQCNMR measurements confirm MDM2 binding.
Keywords: 1H,15NHSQCNMR; indole; macrocycles; multicomponent; p53-MDM2; Ugi reaction; Introduction
Macrocycles are the chemical entities that are consisting of a 12-membered or even bigger
(Scheme 3).
In order to exclude false positive hits, two biorthogonal assays were chosen; 1H,15NHSQCNMR and fluorescence polarization (FP, Table 1). FP assay was employed to determine the inhibitory affinities (Ki) of the derivatives against MDM2 as previously described [36]. Besides 2h (Ki = 2.3 μΜ, Kd
the size number of the macrocycle.
Measurement of Ki and Kd of the selected macrocycles based on FP and 1H,15NHSQCNMR assays, respectively.a
Supporting Information
Supporting Information File 54: Experimental procedures, analytical data, NMR spectra, fluorescence polarization binding assays, 1H,15N
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Graphical Abstract
Scheme 1:
MCR approach to indole-based macrocycles; a more effective strategy is proposed in this work, based...