Here we present an evaluation of the binding affinity prediction accuracy of the free energy calculation method FEP+ on internal active drug discovery projects and on a large new public benchmark set. File list (3) download file view on ChemRxiv manuscript.pdf (4.23 MiB) download file view on ChemRxiv supplementary.pdf (0.92 MiB) download file view on ChemRxiv tables.zip (5.99 KiB)

Here we present an evaluation of the binding affinity prediction accuracy of the free energy calculation method FEP+ on internal active drug discovery projects and on a large new public benchmark set.<br>

No abstract

3,4-Epoxy-1-butene, an active metabolite of 1,3-butadiene, was reacted with guanosine, deoxyguanosine and calf thymus DNA. The products were isolated and positively identified using various spectroscopic techniques. Treatment of calf thymus-DNA with 3,4-epoxy-1-butene yielded two N7-guanine adducts of equal stability. Depurination by neutral hydrolysis showed that 7-(2-hydroxy-3-buten-1-yl)guanine (compound I) was formed in greater quantities compared to its regioisomer 7-(1-hydroxy-3-buten-2-yl)guanine (compound II); spontaneous depurination experiments showed that compound I was released in the highest proportion. The circular dichroism spectral studies with R and S 3,4-epoxy-1-butene revealed that the reaction mechanism at aqueous neutral pH media is more similar to SN2-type rather than SN1-type. The HPLC-electrochemical detection method used to carry out the DNA alkylation study provides a rapid and sensitive quantitation of N7 guanine adducts in biological fluids. This serves as a useful tool for further human biomonitoring experiments.

No abstract