Three dinucleotides containing L-isonucleosides at 5＇-end were synthesized by an elegant phosphoramidite one-pot method. Their binding modes with HIV integrase were simulated and their anti-HIV activities in pseudotyped virus system were examined.
RNA interference has been widely used for gene therapy of various infectious diseases and malignant tumors. However, its poor stability in serum has limited further clinic application. Here, we found that stability of siRNA in serum enhanced obviously when 3′-terminus of sense strand （siRNA-pS） was conjugated with peptide, while same conjugation at 3′-terminus of antisense strand brought no such effects. And it was also found that only the peptide residue in siRNA-pS could be cut off by RNase A. All these results indicated that nucleases in serum prefer to invade siRNA duplex through the 3′-end of sense strand.
3-Deazaneplanocin A （3-DNPA, 2）, an antiviral and antitumor agent, has been synthesized in an optimized procedure in 10 steps, with an increased overall yield of 11.2%. Started from 2,4-dihyroxyl-3-nitropyridine, reduction of nitro group and ring closure of imidazole were carried out in one pot, without the separation of diaminopyridine （10）, to give 3-deazapurine （11）. Moreover, the conversion of 6-chloro-3-deazapurine （12） to 6-amino-3-deazapurine （13） and the synthesis of N^6,N^6,N9-tris-Boc-3- deazadenine （16） was promoted by microwave-aid method. Compound 16 benefited the formation of N9 isomer of 3-DNPA in Mitsunobu reaction.
To improve the stability and pharmacokinetic properties,prodrugs of L-ddG（L-2＇,3＇-dideoxy-guanosine）and L-D4G （L-2＇,3＇-dihydro-2＇,3＇-dideoxyguanosine）modified with a series of substituted amino groups at C-6 position of the purine base were designed and synthesized and their anti-HIV activities were evaluated.Compounds 7d and 8g exhibited moderate activity and showed EC_（50）of 42μmol/L and 55μmol/L,respectively.
