Article Details
<i>In silico</i> Study on the Binding Interactions of SSTA and <sup>18</sup>F-SSTA Towards Somatostatin Receptor Subtype 2
Author(s):
David J. Pérez*, Rodrigo S. Razo-Hernández* and Miguel A. Ávila-Rodríguez* Pages 1048 - 1066 ( 19 )
Abstract:
<p>Background: Somatostatin analogs (SSTAs) are versatile drugs that target a group of proteins known as somatostatin receptors. SSTAs are used for the treatment and PET-molecular imaging of Neuro Endocrine Tumors (NET), for they are labeled with the radionuclide <sup>18</sup>F, a positron emitter radionuclide. </p><p> Objective: The aim of this work was to theoretically study the binding interactions of SSTA labeled with <sup>18</sup>F (half-life of 109.7 min) and somatostatin receptor subtype 2. As the labeling of SSTA with <sup>18</sup>F required the use of a prosthetic group, a hydrophilicity enhancer, and a linker, the influence of these traits on the interactions of <sup>18</sup>F-SSTA with the SSTR-2 binding site was studied. </p><p> Methods: The binding modes of <sup>18</sup>F-labeled analogues with SSTR-2 were studied by using protein homology modelling, non-equilibrium molecular dynamics, and molecular docking calculations, by means of three docking software: MVD, MOE, and VINA. </p><p> Results: The results showed the main role of Asp122, Asn276, Phe272 and Phe294 from the SSTR-2 binding site, which form interactions with residues Lys, Trp, Tyr, and Thr from <sup>18</sup>F-labeled somatostatin analogues. </p><p> Conclusion: The interaction between Lys (from 18F-SSTA) and Asp122 (from SSTR-2) was identified as the most energetic and considered the one that drives the binding between <sup>18</sup>F-SSTA and SSTR-2 (the anchor interaction). Despite the presence of prosthetic groups, linkers, and hydrophilicity enhancers, all the studied <sup>18</sup>F-SSTA formed the anchor interaction. The trend in the results agreed with the experimental reports, identifying the main role of Asp122 in the binding of somatostatin-14 to SSTR-2.</p>
Keywords:
Somatostatin analogs, NET, labeling, docking, positron, receptor.
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