New type anti-HIV reagents on the basis of broad substrate specificity of HIV-1 reverse transcriptase

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Attempts to overcome HIV-1 infection have been made on the basis of the points of attack of the HIV-1 life cycle. HIV-1 reverse transcriptase (RT) plays a central role in the HOV-1 life cycle, copying the genetic information in the genomic RNA into a double-stranded DNA form.Azidothymidine (AZT), an inhibitor of HIV-RT,is being used to treat AIDS.As in vitro and in vivo HIV-1 resistance to a number of RT inhibitors has been reported, RT inhibitors are shown to be no longer chemotherapy for AIDS.A kind of diketopiperazine derivatives is found to be a good or pure substrate, which is not a HIV-1 RT inhibitor, for HIV-1 RT in vitro. These results suggest that the diketopiperazine derivative is metabolically converted to a mimic nucleotide derivative in cell, transcripted to HIV-1 cDNA,and incorporated into host DNA.The mechanism of the anti-HIV action with the derivative is not understood so far, however, the new compound may be very important for AIDS chemotherapy.