5GIX

Human serum albumin-Palmitic acid-Fe(Hn3piT)Cl2

Summary for 5GIX

• Entry DOI: 10.2210/pdb5gix/pdb
• Descriptor: Serum albumin, 14-piperidin-1-yl-11-oxa-13$l^{3}-thia-15,16$l^{4}-diaza-12$l^{3}-ferratetracyclo[8.7.0.0^{2,7}.0^{12,16}]heptadeca-1(10),2(7),3,5,8,13,16-heptaene, PALMITIC ACID, ... (4 entities in total)
• Functional Keywords: ferric compound, anticancer mechanism, tumor targeting, therapeutic effect, immune system
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P02768
• Total number of polymer chains: 2
• Total formula weight: 136243.28

Authors

Yang, F.,Qi, J.,Wang, T. (deposition date: 2016-06-25, release date: 2017-07-19, Last modification date: 2023-11-08)

Primary citation

Qi, J.,Gou, Y.,Zhang, Y.,Yang, K.,Chen, S.,Liu, L.,Wu, X.,Wang, T.,Zhang, W.,Yang, F.
Developing Anticancer Ferric Prodrugs Based on the N-Donor Residues of Human Serum Albumin Carrier IIA Subdomain
J. Med. Chem., 59:7497-7511, 2016

PubMed Abstract: To improve the selectivity, delivery, and activity of ferric (Fe) anticancer agents, we design prodrugs based on N-donor residues of the human serum albumin (HSA) carrier IIA subdomain. We synthesized six Fe(III) compounds derived from 2-hydroxy-1-naphthaldehyde thiosemicarbazone (7-12). HSA complex structure revealed that Fe compound binds to the hydrophobic cavity in the HSA IIA subdomain. Lys199 and His242 of HSA replace the two Cl atoms of Fe compound, coordinating with Fe(3+). In vivo data revealed that compound 12 and HSA-12 complex inhibit the growth of the liver tumor and that the HSA-12 complex has stronger targeting ability and therapeutic efficacy than compound 12 alone. In addition, our results have shown that compound 12 and HSA-12 complex induce Bel-7402 cell death possible by several mechanisms.

PubMed: 27441502
DOI: 10.1021/acs.jmedchem.6b00509

Experimental method

X-RAY DIFFRACTION (2.801 Å)