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VOL. 73 (3), 703-746, 2007 ARE ADRENOMEDULLIN POSITIVE MODULATORS NOVEL...
compounds, as those which better fulfilled the interactions’ pattern
exhibited by i52. These results are displayed in Figure 4.
FIGURE 4. Representation of the pattern of interaction between the 27
docking conformers analyzed and the amino acids of S1’ subpocket of
MMP-2 (position in the energy ranking in Autodock is given in parenthesis).
Conserved amino acids are colored yellow. No conserved amino acids are colored
blue. Amino acids that are reported to be able to establish hydrogen bonds are
colored green. Compound i52 from the PDB 1hov is also included as a reference.
Compounds 1n, 2m and 2n were the most promising candidates
to perform MMP-2 inhibition assays, because they showed a similar
S1’ sub-site contacts pattern to that of i52. These interactions
included unique residues to MMP-2, as Ala139, Thr 143, Tyr144, and
Thr145, and were not observed for the other docking conformers.
Figure 5 shows the resulting docking for 1n (blue) superimposed to
i52 (orange).
FIGURE 5. Docking result for 1n (blue) in comparison with i52 (orange)
resolved by NMR. 1n is able to coordinate Zn2+ occupying the same subistes
as i52.
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