6L4K

Human serum albumin-Palmitic acid-Cu compound

Summary for 6L4K

• Entry DOI: 10.2210/pdb6l4k/pdb
• Descriptor: Serum albumin, PALMITIC ACID, 2-bromanyl-9-ethyl-~{N},~{N},7-trimethyl-3-thia-1$l^{4},5,6$l^{4},10-tetraza-2$l^{4}-cupratricyclo[6.4.0.0^{2,6}]dodeca-1(8),4,6,9,11-pentaen-4-amine (3 entities in total)
• Functional Keywords: complex, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 135900.57

Authors

Zhang, Z.L. (deposition date: 2019-10-17, release date: 2020-10-21, Last modification date: 2024-10-30)

Primary citation

Zhang, Z.,Yu, P.,Gou, Y.,Zhang, J.,Li, S.,Cai, M.,Sun, H.,Yang, F.,Liang, H.
Novel Brain-Tumor-Inhibiting Copper(II) Compound Based on a Human Serum Albumin (HSA)-Cell Penetrating Peptide Conjugate.
J.Med.Chem., 62:10630-10644, 2019

PubMed Abstract: It is a great challenge to design drugs that penetrate the blood-brain barrier to inhibit brain tumor growth by acting against multiple targets and also improve their delivery efficacy and targeting ability to cancer cells. To overcome the above problems, we designed a multitarget metal agent for treating brain tumors based on an human serum albumin (HSA)-cell penetrating peptide conjugate. Thus, we rationally screened copper (Cu) and 2-acetyl-3-ethylpyrazine thiosemicarbazones to synthesize six compounds, and we investigated their structure-activity relationships and confirmed multiple mechanisms for brain glioma cells. The HSA- complex structure indicated that binds to the IIA subdomain of HSA and His242 replaces the Br ligand in in coordination with Cu. In vivo data suggested that both and the HSA--peptide conjugate penetrate the blood-brain barrier and inhibit brain tumor growth with few side effects. Furthermore, the HSA-peptide conjugate also improved the delivery efficacy and targeting ability of in vivo.

PubMed: 31693353
DOI: 10.1021/acs.jmedchem.9b00939

Experimental method

X-RAY DIFFRACTION (2.09 Å)