5T4F

Human DPP4 in complex with ligand 34p

5T4F の概要

• エントリーDOI: 10.2210/pdb5t4f/pdb
• 関連するPDBエントリー: 5T4B 5T4E 5T4H
• 分子名称: Dipeptidyl peptidase 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: structure-based drug design, diabetes, dpp4 inhibitors, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 174340.52

構造登録者

Scapin, G. (登録日: 2016-08-29, 公開日: 2016-10-05, 最終更新日: 2024-10-30)

主引用文献

Pissarnitski, D.A.,Zhao, Z.,Cole, D.,Wu, W.L.,Domalski, M.,Clader, J.W.,Scapin, G.,Voigt, J.,Soriano, A.,Kelly, T.,Powles, M.A.,Yao, Z.,Burnett, D.A.
Scaffold-hopping from xanthines to tricyclic guanines: A case study of dipeptidyl peptidase 4 (DPP4) inhibitors.
Bioorg.Med.Chem., 24:5534-5545, 2016

PubMed Abstract: Molecular modeling of unbound tricyclic guanine scaffolds indicated that they can serve as effective bioisosteric replacements of xanthines. This notion was further confirmed by a combination of X-ray crystallography and SAR studies, indicating that tricyclic guanine DPP4 inhibitors mimic the binding mode of xanthine inhibitors, exemplified by linagliptin. Realization of the bioisosteric relationship between these scaffolds potentially will lead to a wider application of cyclic guanines as xanthine replacements in drug discovery programs for a variety of biological targets. Newly designed DPP4 inhibitors achieved sub-nanomolar potency range and demonstrated oral activity in vivo in mouse glucose tolerance test.

PubMed: 27670099
DOI: 10.1016/j.bmc.2016.09.007

実験手法

X-RAY DIFFRACTION (1.9 Å)