Design an anticancer copper(II) pro-drug based on the flexible IIA subdomain of human serum albumin.

Design an anticancer copper(II) pro-drug based on the flexible IIA subdomain of human serum albumin. J Inorg Biochem. 2017 Apr 04;172:1-8 Authors: Zhang Y, Zhang Z, Gou Y, Jiang M, Khan H, Zhou Z, Liang H, Yang F Abstract Owing to the flexible IIA sub-domain of human serum albumin (HSA), we proposed to rationally design a metal agent with a leaving group, and then regulate a leaving group of metal agent to be displaced by His-242 for improving its delivery efficiency and selectivity. To confirm our hypothesis, we synthesized a copper(II) compound derived from 2-amino-5-chlorophenol 2-hydroxybenzaldehyde Schiff-base, containing a leaving group [pyridine, PRD], namely Cu(L)(PRD). The HSA complex structure revealed that Cu(L)(PRD) binds to the hydrophobic cavity in HSA IIA sub-domain, His242 of HSA replaces the pyridine ligand in Cu compound, coordinating with Cu(2+). HSA complex enhances cytotoxicity by about 1.4-fold in cancer cells but has no effect on normal cells in vitro through selectively accumulating into cancer cells. Interestingly, HSA complex has stronger anticancer capacity relative to unbound Cu(L)(PRD). PMID: 28395195 [PubMed - as supplied by publisher]
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research