دورية أكاديمية
أعرض في EDS

Molecular Determinants of EphA2 and EphB2 Antagonism Enable the Design of Ligands with Improved Selectivity.

التفاصيل البيبلوغرافية
العنوان: Molecular Determinants of EphA2 and EphB2 Antagonism Enable the Design of Ligands with Improved Selectivity.
المؤلفون: Guidetti L; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Zappia A; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Scalvini L; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Ferrari FR; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Giorgio C; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Castelli R; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Galvani F; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Vacondio F; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Rivara S; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Mor M; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy.; Microbiome Research Hub, Università degli Studi di Parma, Parco Area delle scienze 11/A, I- 43124 Parma, Italy., Urbinati C; Dipartimento di Medicina Molecolare Traslazionale, Università degli Studi di Brescia, Brescia 25121, Italy., Rusnati M; Dipartimento di Medicina Molecolare Traslazionale, Università degli Studi di Brescia, Brescia 25121, Italy., Tognolini M; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy., Lodola A; Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I- 43124 Parma, Italy.
المصدر: Journal of chemical information and modeling [J Chem Inf Model] 2023 Nov 13; Vol. 63 (21), pp. 6900-6911. Date of Electronic Publication: 2023 Nov 01.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101230060 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-960X (Electronic) Linking ISSN: 15499596 NLM ISO Abbreviation: J Chem Inf Model Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society, c2005-
مواضيع طبية MeSH: Receptor, EphA2*/antagonists & inhibitors , Receptor, EphB2*/antagonists & inhibitors, Humans ; Ligands ; Molecular Dynamics Simulation ; Protein Binding
مستخلص: With the aim of identifying novel antagonists selective for the EphA receptor family, a combined experimental and computational approach was taken to investigate the molecular basis of the recognition between a prototypical Eph-ephrin antagonist (UniPR1447) and two representative receptors of the EphA and EphB subfamilies, namely, EphA2 and EphB2 receptors. The conformational free-energy surface (FES) of the binding state of UniPR1447 within the ligand binding domain of EphA2 and EphB2, reconstructed from molecular dynamics (MD) simulations performed on the microsecond time scale, was exploited to drive the design and synthesis of a novel antagonist selective for EphA2 over the EphB2 receptor. The availability of compounds with this pharmacological profile will help discriminate the importance of these two receptors in the insurgence and progression of cancer.
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المشرفين على المادة: 0 (Ligands)
EC 2.7.10.1 (Receptor, EphA2)
EC 2.7.10.1 (Receptor, EphB2)
تواريخ الأحداث: Date Created: 20231101 Date Completed: 20231128 Latest Revision: 20231128
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10647059
DOI: 10.1021/acs.jcim.3c01064
PMID: 37910792
قاعدة البيانات: MEDLINE
الوصف
تدمد:1549-960X
DOI:10.1021/acs.jcim.3c01064