Selective Targeting of the Zinc Finger Domain of HIV Nucleocapsid Protein NCp7 with Ruthenium Complexes. Issue 72 (20th November 2018)

• Record Type: Journal Article
• Authors: Sheng, Yaping; Cao, Kaiming; Li, Ji; Hou, Zhuanghao; Yuan, Siming; Huang, Guangming; Liu, Hongke; Liu, Yangzhong
• Is Part Of: Chemistry. Volume 24:Issue 72(2018)
• Page Start: 19146
• Page End: 19151
• Publication Date: 2018-11-20
• Subjects: ligand design -- drug design -- metallodrugs -- NCp7 -- Ru-based drugs -- zinc finger; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201803917
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Nucleocapsid protein 7 (NCp7) is an attractive target for anti‐HIV drug development. Here we found that ruthenium complexes are reactive to NCp7 and various Ru‐agents exhibit significantly different reactivity. Interestingly, the zinc‐finger domains of NCp7 also demonstrate different affinity to Ru‐complexes; the C‐terminal domain is much more reactive than the N‐terminal domain. Each zinc‐finger domain of NCp7 binds up to three Ru‐motifs, and the ruthenium binding causes zinc‐ejection from NCp7 and disrupts the protein folding. Therefore, ruthenium complexes interfere with the DNA binding of NCp7 and interrupt the protein function. The different reactivity of Ru‐agents suggests a feasible strategy for improving the targeting of NCp7 by ligand design. This work provides an insight into the mechanism of ruthenium complex with NCp7, and suggests more potential application of ruthenium drugs. Abstract : Ruthenium complexes are reactive to NCp7 and exhibit significantly different reactivity. Ruthenium binding results in zinc‐ejection from NCp7 and disrupts recognition of the protein to nucleic acids. In addition, the C‐terminal domain of NCp7 is much more reactive than the N‐terminal domain to ruthenium complexes. This work found a new type of inhibitors of NCp7. The different reactivity of the ruthenium complex suggests that targeting NCp7 could be modulated by ligand modification.