7Y2D

HSA-Cu agent complex

Summary for 7Y2D

• Entry DOI: 10.2210/pdb7y2d/pdb
• Descriptor: Serum albumin, PALMITIC ACID, 13-methoxy-~{N},~{N}-dimethyl-2-oxa-4-thia-6,7$l^{4}-diaza-3$l^{3}-cupratricyclo[7.4.0.0^{3,7}]trideca-1(9),5,7,10,12-pentaen-5-amine, ... (4 entities in total)
• Functional Keywords: complex, metal binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 68383.09

Authors

Zhang, Z.L.,Yang, F. (deposition date: 2022-06-09, release date: 2023-07-05, Last modification date: 2025-08-20)

Primary citation

Jiang, M.,Zhang, Z.,Li, W.,Man, X.,Sun, H.,Liang, H.,Yang, F.
Developing a Copper(II) Agent Based on His-146 and His-242 Residues of Human Serum Albumin Nanoparticles: Integration To Overcome Cisplatin Resistance and Inhibit the Metastasis of Nonsmall Cell Lung Cancer.
J.Med.Chem., 65:9447-9458, 2022

PubMed Abstract: To overcome the resistance of nonsmall cell lung cancer (NSCLC) cells to cisplatin and inhibit their metastasis, we proposed to develop a Cu(II) agent based on the specific residue(s) of HSA nanoparticles (NPs) for multitargeting the tumor microenvironment (TME). To this end, we not only synthesized four Cu(II) 2-hydroxy-3-methoxybenzaldehyde thiosemicarbazone compounds (C1-C4), obtaining a Cu compound (C4) with significant cytotoxicity by studying their structure-activity relationships, but also revealed the binding mechanism of C4 to HSA through X-ray crystallography and confirmed the successful construction of a new HSA-C4 NPs delivery system. C4 and HSA-C4 NPs inhibited the A549cisR tumor growth and metastasis, and HSA NPs optimized the anticancer behavior of C4. We further confirmed the anticancer mechanism of the C4/HSA-C4 NP multitargeting TME to overcome cisplatin resistance: killing tumor cells by acting on the mtDNA and inducing apoptosis, polarizing M2-type macrophages to the M1-type, and inhibiting angiogenesis.

PubMed: 35786921
DOI: 10.1021/acs.jmedchem.2c00698

Experimental method

X-RAY DIFFRACTION (2 Å)