Construction of a genetically engineered chimeric apoprotein consisting of sequences derived from lidamycin and neocarzinostatin.

Wenguo Jiang, Boyang Shang, Liang Li, Shenghua Zhang, Yongsu Zhen

Anti-cancer drugs 2016 Jan

filter terms:

Neocarzinostatin (NCS) consists of an enediyne chromophore and an apoprotein (NCP). Lidamycin (LDM) is composed of another active enediyne chromophore (AE) and an acidic protein (LDP). Although the structures of NCP and LDP are very similar, LDM has been shown to have an increased tumor-suppressive activity than that of NCS. The aim of this study was to construct a chimeric protein (CMP) that consists of both the terminus residue of NCP and an LDP pocket-forming residue that can bind AE. This CMP will have a structure similar to NCS and an antitumor activity similar to LDM. The assembling efficiency of LDP, CMP, and NCP was 73.9, 1.5, and 1.1%, respectively. The cytotoxicity was consistent with their assembling efficiency of AE in proteins. When CMP-AE and NCP-AE were administered at equivalent AE doses of LDM, the inhibition rate of CMP-AE was the same as LDM and significantly higher than that of NCP-AE. Our study implied that the binding activity between LDP and AE was very specific. The terminus residue of LDP could affect the specifically binding activity. The pocket-forming residue could confer a protective function to the chromophore. Further investigation of its bioactivity might serve as a new drug design strategy and drug-delivery carrier in targeted cancer therapy.

Citation

Wenguo Jiang, Boyang Shang, Liang Li, Shenghua Zhang, Yongsu Zhen. Construction of a genetically engineered chimeric apoprotein consisting of sequences derived from lidamycin and neocarzinostatin. Anti-cancer drugs. 2016 Jan;27(1):24-8