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Anastasia Yu. Mikhailova, Ulyana A. Budanova, Yurii L. Sebyakin
Modeling
of the interaction of low molecular weight targeting ligands and synthesis of
lipotripeptides with potential inhibitory ability against integrin αVβ3
Abstract
Abstract. Low molecular weight RGD peptides and RGD mimetics are widely
studied as ligands targeting the corresponding receptor in the diagnosis and
therapy of cancer, as well as in the field of bone tissue regeneration. Some of
them are undergoing preclinical trials. The aim of this work is to select
optimal variants of the ligand structure based on an aliphatic RGD mimetic. By
methods of molecular modeling (“blind” docking and active site docking), the
most advantageous constructions for the formation of a stable complex with the
integrin αVβ3 were determined. A scheme was developed and
the synthesis of two lipotripeptides Gnd-GABA-Gly-Asp(C16)2,
Gnd-β-Ala-Gly-Asp(C16)2 with the potential ability to inhibit
this receptor on the surface of tumor tissues was carried out.
Key words: molecular docking, RGD peptides, RGD mimetics, integrins, integrin αVβ3,
lipotripeptides
Copyright (C) Chemistry Dept., Moscow State University, 2002
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