Abstract
Diorganotin(IV) antitumor compound bis-[2,6-difluoro-N-(hydroxyl-<κ>O)benzamidato-<κ>O] (DBDF2,6T) was one of the novel patent organotin compounds with high antitumor activity and relatively low toxicity. In this study, several methods were used to study the interaction between DBDF2,6T and hPPARγ protein, including fluorescence quenching, three-dimensional (3D) fluorescence, drug affinity responsive target stability (DARTS), ultrafiltration-LC, and molecular docking. According to the experimental results, the quenching process of the hPPARγ protein was induced by static quenching mode to form a nonradiative ground-state complex with DBDF2,6T spontaneously, mainly through the hydrophobic force. DBDF2,6T could bind to the hPPARγ protein directly and give the protein the ability of antienzymatic hydrolysis. And the binding mode of DBDF2,6T into hPPARγ protein appeared to have an orientation towards residues of SER342 and GLY284. In conclusion, these methods could comprehensively reveal the interaction details of DBDF2,6T and the hPPARγ protein and established a feasible way to preliminarily identify the agonist compounds for the hPPARγ protein.
Highlights
Organotin compounds have many uses in our life, which could act as stabilizers in plastics, fungicides, industrial catalysts, and so on. [1]
From the results of proteomics data, these compounds might play the physiological role through the PPAR signaling pathway, which was consistent with the reports that organotin compounds may function as endocrine-disrupting chemicals by affecting the function of the protein PPARc [3]
When the PPARs proteins bind to a specific ligand, the ligand-binding domains of PPARs will encounter the conformational change followed by promoting the recruitment of nuclear receptor coregulators such as steroid rector coactivator-1 (SRC-1) and eventually influence the transcription of downstream target genes [5]. e PPARs proteins have three isotypes which had been identified as PPARα, PPARβ/δ, and PPARc. ese three subtypes exhibit distinct tissue distributions and have unique biological functions [6, 7]
Summary
Organotin compounds have many uses in our life, which could act as stabilizers in plastics, fungicides, industrial catalysts, and so on. [1]. Several di erent methods were adopted to test and verify the interaction between DBDF2,6T and the hPPARc protein.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
