7DOC

Crystal structure of Zika NS2B-NS3 protease with compound 5

7DOC の概要

• エントリーDOI: 10.2210/pdb7doc/pdb
• 分子名称: Core protein, Genome polyprotein, Serine protease subunit NS2B, ... (9 entities in total)
• 機能のキーワード: viral protease, protease inhibitor complex, viral protein
• 由来する生物種: Zika virus (ZIKV); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 83956.59

構造登録者

Quek, J.P. (登録日: 2020-12-14, 公開日: 2021-04-14, 最終更新日: 2024-07-10)

主引用文献

Patil, N.A.,Quek, J.P.,Schroeder, B.,Morewood, R.,Rademann, J.,Luo, D.,Nitsche, C.
2-Cyanoisonicotinamide Conjugation: A Facile Approach to Generate Potent Peptide Inhibitors of the Zika Virus Protease.
Acs Med.Chem.Lett., 12:732-737, 2021

PubMed Abstract: The rapid generation and modification of macrocyclic peptides in medicinal chemistry is an ever-growing area that can present various synthetic challenges. The reaction between N-terminal cysteine and 2-cyanoisonicotinamide is a new biocompatible click reaction that allows rapid access to macrocyclic peptides. Importantly, 2-cyanoisonicotinamide can be attached to different linkers directly during solid-phase peptide synthesis. The synthesis involves only commercially available precursors, allowing for a fully automated process. We demonstrate the approach for four cyclic peptide ligands of the Zika virus protease NS2B-NS3. Although all peptides display the substrate recognition motif, the activity strongly depends on the linker length, with the shortest cyclization linker corresponding to highest activity ( = 0.64 μM). The most active cyclic peptide displays affinity 78 times higher than that of its linear analogue. We solved a crystal structure of the proteolytically cleaved ligand and synthesized it by applying the presented chemistry to peptide ligation.

PubMed: 34055219
DOI: 10.1021/acsmedchemlett.0c00657

実験手法

X-RAY DIFFRACTION (1.904 Å)