Role of single-electron reduction potential in inhibition of reverse transcriptase by streptonigrin and sakyomicin A.
نویسندگان
چکیده
Streptonigrin was first isolated from Streptomyces flocculus as an antitumor antibiotici;). Later, the antibiotic was recognized to be a potent inhibitor of avian myeloblastosis virus (AMV) reverse transcriptase2). Recently, we reported that streptonigrin inhibited AMV reverse transcriptase mainly by interacting with an enzyme molecule3). According to the results of the kinetic analysis, streptonigrin inhibited reverse transcriptase in a non-competitive manner. As reported previously4~6), the cytotoxicity of streptonigrin results in part from its bypassing effect on the mitochondrial oxidative phosphorylation. In the presence of catalytic amounts of streptonigrin, DT-diaphorase catalyzes the oxidation of NADHsupplied by the mitochondrial redox system. The hydroquinone of streptonigrin formed in conjunction with the oxidation of NADHin turn autoxidizes to the quinone by transferring electrons to molecular oxygen. The electron-acceptor activity of streptonigrin was also observed in the oxidation of NADH by Clostridium kluyveri diaphorase6). Like streptonigrin, sakyomicin A is a quinone antibiotic with an inhibitory activity against reverse transcriptase7» 8) , though the latter is less active than the former. Sakyomicin A played the role of electron acceptor in the oxidation of NADH by both mitochondrial and C. kluyveri diaphorase, as in the case of streptonigrin6»8). Further, we ob-
منابع مشابه
Comparative studies of the inhibitory properties of antibiotics on human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases and cellular DNA polymerases.
The inhibition of human immunodeficiency virus (HIV) reverse transcriptase by certain antibiotics and related compounds was studied in comparison with that of avian myeloblastosis virus (AMV) reverse transcriptase and cellular DNA polymerases alpha and beta. In general, compounds that inhibited HIV reverse transcriptase also inhibited AMV reverse transcriptase. For example, 10 micrograms/ml of ...
متن کاملRole of the naphthoquinone moiety in the biological activities of sakyomicin A.
The naphthoquinone moiety was proven to be essential to the biological activities of sakyomicin A using various naphthoquinone derivatives. Among the naphthoquinones tested, juglone (5-hydroxy-1,4-naphthoquinone) which resembles the partial structure of sakyomicin A was the most active in cytotoxicity against murine lymphosarcoma L5178Y cells, electron acceptor function in the oxidation of NADH...
متن کاملKinetic analysis of inhibition of reverse transcriptase by streptonigrin.
The antitumor antibiotic, streptonigrin (1), was first isolated from Streptomyces flocculus1^. Later, the inhibition of avian myeloblastosis virus (AMV) reverse transcriptase by 1 was reported by Chirigos et al.2\ while no inhibition was observed with methyl streptonigrin (2), suggesting the importance of the carboxyl group for this activity. To confirm this aspect, the biological properties of...
متن کاملBiological properties of streptonigrin derivatives. II. Inhibition of reverse transcriptase activity.
Reverse transcriptase of RNA tumor viruses plays an important role in the integration of the viral genome into host cell DNA1,2) and specific inhibitors of this enzyme might provide chemotherapeutic agents against infection by retro viruses. In the course of our screening for enzyme inhibitors against reverse transcriptase of avian myeloblastosis virus (AMV), the novel substances, retrostatin3)...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of antibiotics
دوره 40 5 شماره
صفحات -
تاریخ انتشار 1987