期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 712, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2021.109042
关键词
Single-stranded polyriboadenylic acid; RNA-Alkaloid interaction; Self-assembly; Cooperative binding
资金
- UGC, Government of India
Research has shown that cryptolepine can induce self-assembly and alter the structural conformation of single-stranded polyriboadenylic acid upon binding, potentially providing an opportunity to develop novel alkaloid-based chemotherapeutic agents.
RNAs have become a well-known target for chemotherapeutic agents in the recent years. The tails of most eukaryotic m-RNA are characterized by the presence of a long polyadenylate sequence which plays an important role in its growth and maturation. This lays emphasis on development of molecular probes that target the polyadenylate sequence. Cryptolepine (hereafter, CRP) is an indoloquinoline alkaloid well known for its antimalarial activities. A series of spectroscopic experiments namely absorption studies, fluorimetric studies and circular dichroism studies show that cryptolepine binds with single-stranded polyriboadenylic acid (hereafter, sspoly (rA)) with a binding constant of similar to 5 x 10(3) M-1 at 25 degrees C. Moreover thermal denaturation experiments show that the bound form of polyriboadenylic acid shows a characteristic transition profile. Such a profile is indicative of the ability of cryptolepine to induce self-assembly in the polyriboadenylic acid sequence on binding to it. Such ability of CRP to modulate the structural conformation of poly (rA), which in turn may cause functional aspects of the RNA to change, may give us a chance to develop effective alkaloid based chemotherapeutic agents.
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