木虫 (正式写手)
早起哒虫砸有鸟吃(⊙o⊙) ![]()
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小木虫: 金币+0.5, 给个红包，谢谢回帖
千乐: 金币+5, 谢谢大侠啦~ 2014-11-30 15:47:18
P-GP的底物大都是CATIONIC HYDROPHOBIC 的化合物。
推荐几个：
A computational ensemble pharmacophore model for identifying substrates of P-glycoprotein.Penzotti JE, Lamb ML, Evensen E, Grootenhuis PD.
P-glycoprotein (P-gp) functions as a drug efflux pump, mediating multidrug resistance and limiting the efficacy of many drugs. Clearly, identification of potential P-gp substrate liability early in the drug discovery process would be advantageous. We describe a multiple-pharmacophore model that can discriminate between substrates and nonsubstrates of P-gp with an accuracy of 63%. The application of this filter allows large virtual libraries to be screened efficiently for compounds less likely to be transported by P-gp.
PMID: 11960484 [PubMed - indexed for MEDLINE]
A general pattern for substrate recognition by P-glycoprotein.Seelig A.
Department of Biophysical Chemistry, Biocenter of the University of Basel, Switzerland. seeliga@ubaclu.unibas.ch
P-glycoprotein actively transports a wide variety of chemically diverse compounds out of the cell. Based on a comparison of a hundred compounds previously tested as P-glycoprotein substrates, we suggest that a set of well-defined structural elements is required for an interaction with P-glycoprotein. The recognition elements are formed by two (type I unit) or three electron donor groups (type II unit) with a fixed spatial separation. Type I units consist of two electron donor groups with a spatial separation of 2.5 +/- 0.3 A. Type II units contain either two electron donor groups with a spatial separation of 4.6 +/- 0.6 A or three electron donor groups with a spatial separation of the outer two groups of 4.6 +/- 0.6 A. All molecules that contain at least one type I or one type II unit are predicted to be P-glycoprotein substrates. The binding to P-glycoprotein increases with the strength and the number of electron donor or hydrogen bonding acceptor groups forming the type I and type II units. Correspondingly, a high percentage of amino acids with hydrogen bonding donor side chains is found in the transmembrane sequences of P-glycoprotein relevant for substrate interaction. Molecules that minimally contain one type II unit are predicted to be inducers of P-glycoprotein over-expression.
PMID: 9492291 [PubMed - indexed for MEDLINE] |
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