|
Zinc finger inhibitors, or zinc ejectors, are substances or compounds that interact adversely with zinc fingers and cause them to release their zinc from its binding site, disrupting the conformation of the polypeptide chain and rendering the zinc fingers ineffective, thereby preventing them from performing their associated cellular functions. This is typically accomplished through chelation of the zinc binding site. As zinc fingers are known to be involved in m-RNA regulation, reverse transcription, protection of synthesized viral DNA, transcription inhibition, and initial integration processes, prevention of zinc finger function can have drastic effects on the function of the cell or virus. Zinc finger inhibitors are typically used to combat HIV. HIV treatments usually rely on targeting reverse transcriptases and proteases. However, these methods are proving to be ineffective due to the development of resistant strains of the virus or due to the stoppage of the treatment. This method of using zinc finger inhibitors to target and destabilize zinc fingers represents a new method of fighting HIV. Other viruses such as SARS, polio, Ebola, measles, human coxsackie, Dengue, rabies, human hepatitis, human parainfluenza and human respiratory syncytical have similar zinc finger motifs and could potentially benefit from zinc finger inhibitor technology.〔 Zinc ejectors were patented in 2008〔 and some have entered Phase I/II trials as a HIV drug. ==Zinc Finger Inhibitor Target: Nucleocapsid Protein== The HIV-1 nucleocapsid protein 7 (NCp7) is the protein targeted by zinc ejectors. NCp7 is initially formed as part of the gag polypeptide and follows a gag-knuckle zinc finger conformation. In its lifetime, NCp7 facilitates the unwinding of tRNA, acts as a primer for reverse transcription, chaperones nucleic acids within the capsid of HIV-1, helps integrate the viral RNA into budding virions, and is intimately involved in the replication of HIV-1 in both the early phase and late phase.〔 〔 These processes play critical roles in the replication of HIV-1 thus making NCp7 a prime target for drugs seeking to contravene the replication process. NCp7 is a 55-amino acid protein that is highly basic and consists of two gag-knuckle motifs. These motifs contain two peptide units of Cys-X2-Cys-X4-His-X4-Cys (CCHC), where the X represents a substituted amino acid, that make up the zinc (II) ion binding sites. The binding of zinc (II) in the CCHC binding site is necessary for the domain to be functional and for the stabilization of the conformation of the structure, allowing the NCp7 to carry out the processes required for HIV replication. Since the CCHC binding site is mutation resistant and involved in the replication of HIV-1, it makes a prime candidate for the prevention of HIV through zinc ejectors.〔 By inhibiting the function of NCp7, the viral replication is affected and a non-functional virus that is unable to infect its host is produced. 抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)』 ■ウィキペディアで「Zinc finger inhibitor」の詳細全文を読む スポンサード リンク
|