Fig 1.
Structures of peptidomimetic ligands 1 and 2.
Fig 2.
The binding epitope of compounds 1 and 2 in the presence of wt E-cadherin-EC1-EC2.
The dots on the structure indicate the ligand binding epitope at different temperatures (left, blu 283K, green 290K and red 298K). The histogram shows the comparison of absolute STD % at different temperatures (right).
Fig 3.
Comparison between the epitopes of compound 1 in the presence of wt and truncated E-cadherin.
A) 1H-NMR at 283K of compound 1. B) and C) STD-NMR at 283K of compound 1 in the presence of wt E-cadherin-EC1-EC2 and E-cadherin-(Val3)-EC1-EC2, respectively. The interacting protons are marked.
Fig 4.
Docking binding mode of the compound 1 into E-cadherin.
The ligand (grey carbon atoms) is superimposed to the DWVI sequence (light blue) of the E-cadherin X-ray crystal structure (PDB code: 3Q2V). Residues of the binding pocket interacting with the ligand are labelled.
Table 1.
List of protein residues close to the NH10, NH1, NHIle protons of 1 in MD simulations at 300 K and 320 K, ranked according to their most populated contact.
Only the percentage value of the most and the least populated contacts is reported.
Fig 5.
Docking preferred binding modes of compound 2 into E-cadherin.
Type A is shown for the ligand charged state (left) and type B for the ligand neutral state. The compound (grey carbon atoms) is displayed into the E-cadherin X-ray structure (PDB code: 3Q2V) superimposed to the DWVI sequence (light blue). Residues of the binding pocket interacting with the ligand are labelled.
Table 2.
Populations of ligand-protein hydrogen bonds in MD simulations at 300 K (left) and 320 K (right) for compound 2 (neutral form).
The hydrogen bonds of the starting structure (binding mode A) are highlighted in bold.
Table 3.
List of protein residues close to the NH19 and NH2 protons of 2 in MD simulations at 300 K and 320 K.
Only the percentage values of the most and the least populated contacts are reported.