A. Yu. Mikhailova, U. A. Budanova, Yu. L. Sebyakin
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引用次数: 0
摘要
低分子量RGD肽和RGD模拟物作为靶向相应受体的配体在癌症的诊断和治疗以及骨组织再生领域得到了广泛的研究。其中一些正在进行临床前试验。本研究的目的是选择基于脂肪族RGD模拟的配体结构的最佳变体。通过分子模拟(盲对接和活性位点对接)的方法，确定了与整合素αVβ3形成稳定配合物的最有利结构。我们提出了一种方案，合成了两个具有抑制肿瘤组织表面该受体的潜在能力的脂三肽Gnd- gaba - gly - asp (C16)2和Gnd-β-Ala-Gly-Asp(C16)2。
Modeling the Interaction of Low Molecular Weight Targeting Ligands and Synthesis of Lipotripeptides with Potential Inhibitory Ability Against Integrin αVβ3
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 study is to select the 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 are determined. A scheme is developed and two lipotripeptides Gnd-GABA-Gly-Asp(C16)2 and Gnd-β-Ala-Gly-Asp(C16)2 with the potential ability to inhibit this receptor on the surface of tumor tissues are synthesized.
期刊介绍：
Moscow University Chemistry Bulletin is a journal that publishes review articles, original research articles, and short communications on various areas of basic and applied research in chemistry, including medical chemistry and pharmacology.
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