Structure-activity relationships of pyrimidine nucleosides as antiviral agents for human immunodeficiency virus type 1 in peripheral blood mononuclear cells.

The structure-activity relationships of several pyrimidine nucleosides related to 3'-azido-3'-deoxythymidine (AZT) were determined in human immunodeficiency virus type 1 (HIV-1) infected human peripheral blood mononuclear cells. These studies indicated that nucleosides with a 3'-azido group on the sugar ring exhibited the most potent antiviral activity. Substitution at C-5 with H, CH3, and C2H5 produced derivatives with the highest potency, whereas alkyl functions greater than C2, including bromovinyl substitution reduced the antiviral potency significantly. Changing the 3'-azido function to an amino or iodo group reduced the antiviral activity. Replacement of the uracil ring by cytosine or 5-methylcytosine produced analogues with high potency and low toxicity. Modification of the 5'-hydroxy group markedly reduced the antiviral activity. Similarly, various C-nucleoside analogues related to AZT and 2',3'-dideoxycytidine were inactive and nontoxic. From these systematic studies 3'-azido-2',3'-dideoxyuridine (5a), 3'-azido-5-ethyl-2',3'-dideoxyuridine (5c), and 3'-azido-2',3'-dideoxycytidine (7a) and its 5-methyl analogue (7b) were identified as potent and selective anti-HIV-1 agent in primary human lymphocytes.

Optimal immobilization of penicillinase for lon-selective electrode.

Penicillin sensor was prepared by immobilizing penicillinase (Pcase) on H(+)-selective carboxylated poly (vinyl chloride) (PVC-COOH) membrane or cellulose filter membrane. The immobilization techniques are as follows. Pcase was immobilized with GTH on H(+)-selective PVC-COOH membrane or some amount of BSA was dropped on that membrane. Another method to make immobilization is to mix type I Pcase with GTH and drop on a cellulose filter membrane. According to immobilization techniques, there were some differences in response properties of enzyme electrodes, however, all electrodes responded to Pcase-resistant penicillin derivatives. Pcase immobilized on cellulose filter membrane with H(+)-selective PVC membrane eletrode was more stable and more sensitive to penicillinase-resistant penicillin derivatives than any other immobilization techniques.