PREDICTIVE IDENTIFICATION OF PENTABROMOCYCLODODECENE (PBCD)ISOMERS WITH HIGH BINDING AFFINITY TO hTTR

摘要：

The binding affinities of the six main hexabromocyclododecane (HBCD) stereoisomers and all of their possible 48 allylic pentabromocyclododecene (PBCD) metabolites to the endocrinous human transthyretin receptor (hTTR) were investigated and compared to the natural binder thyroxine, and the two brominated diphenyl ethers BDE-47 and 3-hydroxy-BDE-47. The endocrine disrupting potency was approximated by a combination of two methods: a surface matching with the natural binder thyroxine (T4) followed by approximation of free binding energies for various binding modes within hTTR. The results indicate slightly higher binding affinities for both BDE structures than for T4 itself and similarly high affinities for two trans-configurated PBCD isomers. For many other PBCD isomers, intermediate values were computed, whereas all HBCD diastereomers yielded significantly lower binding affinities.

作者: Weber M Durmaz V Becker R Esslinger S

作者单位: Zuse Institute Berlin (ZIB),Computational Drug Design,14195 Berlin,Germany BAM Federal Institute for Materials Research and Testing,12489 Berlin,Germany

会议类型: 国际会议

会议名称: 29th International Symposium on Halogenated Persistent Organic Pollutants(第29届国际持久性有机污染物研讨会)(2009国际二噁英大会)

会议地点: 北京

会议语种:英文

页码: 1-6

在线出版日期: 2009-08-24（万方平台首次上网日期，不代表论文的发表时间）