Preparation and affinity identification of glutamic acid-urea small molecule analogs in prostate cancer

Zhang, Zhiwei; Zhu, Zheng; Yang, Deyong; Fan, Weiwei; Wang, Jianbo; Li, Xiancheng; Chen, Xiaochi; Wang, Qifeng; Song, Xishuang

doi:10.3892/ol.2016.4699

Cited by 7 publications

(1 citation statement)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Urea-based SMI (Glu-urea-R) have demonstrated to specifically bind to PSMA and inhibit its activity in the LNCaP cell line. In such compounds, Glu-urea is the binding terminal and the R-group is the coupling terminal to other chemical groups such as a linker and a chelator associated with radionuclides [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Nuclei Near and Far From β -Stability Line

Nayak¹,

Sahoo²,

Acharya³

2015

JNP

View full text Add to dashboard Cite

The prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane glycoprotein with enzymatic activity similar to the family of zinc-dependent exopeptidases. This protein is of great medical and pharmacological interest as overexpression in prostate cells is related to the progression of prostate cancer; therefore, it represents an important target for the design of radiopharmaceuticals. The presence of two Zn 2+ ions in the active site is crucial to the enzymatic activity and the design of high-affinity inhibitors. The amino acid residues coordinating these ions are highly conserved in PSMA orthologs from plants to mammals, and site-mutagenesis assays of these residues show a loss of enzymatic function or reduction of the kinetic parameters. In the present work, we performed molecular dynamics simulation of PSMA with the purpose of characterizing it energetically and structurally. We elucidated the differences of PSMA with its two Zn +2 ions as cofactors and without them in the free energy profile, and in four structural parameters: root mean square deviations and root mean square fluctuations by atom and amino acid residue, radius of gyration, and solvent accessible surface area.

show abstract

Section: Introductionmentioning

confidence: 99%