부산대학교 도서관

A number of structurally diverse compounds have been shown to be potent inhibitors of the DNA polymerase activity of human immunodeficiency virus type 1 (HIV‐1) reverse transcriptase (RT). The compounds can be grouped into two broad classes; nucleoside analogs and nonnucleoside RT inhibitors. The nonnucleoside RT inhibitors are quite specific for HIV‐1 RT but not human immunodeficiency virus type 2 (HIV‐2) and simian immunodeficiency virus (SIV) RT. We have investigated the property of SIV/HIV‐1 chimeric viruses in which portions of SIVMACRT were exchanged with the corresponding domain of HIV‐1 RT; amino acids 176‐190, 176‐383 and 176‐495 of HIV‐1 RT. The chimeric virus, which was substituted amino acids 176‐190 of RT, had detectable RT activity, and this chimeric RT was sensitive to three nonnucleoside RT inhibitors [nevirapine, HEPT derivative (E‐EBU‐dM) and TIBO derivative (R82913)]. To further study this chimeric virus, we purified the chimeric RT enzyme expressed in Escherichia coliand determined its kinetic properties; the Kmand Vmaxvalues, and the Kivalue of HEPT derivative calculated for the DNA polymerase activity. This study reveals that amino acids 176‐190 of SIVMACRT were important for the enzymatic activity and the SIV/HIV‐1 chimeric RT, which had amino acids 176‐190 of HIV‐1, was sensitive to the nonnucleoside RT inhibitor.