We report on the synthesis of a series of peptideAZT (2A, 2B, 5A, 5B) and peptide-(AZT-MP) conjugates incorporating peptide sequences found in a nonapeptide known to be a HIV-PR substrate. We also selected the AZT-MP phosphoramidate peptide-conjugates containing an additional alanine residue directly linked to the phosphorus atom. Indeed, among the various aminoacid phosphoramidates of ddN analogues known so far, the alanine derivative was shown to be one of the most efficient ddN-MP delivery system. All these conjugates contain the scissile Phe-Pro motif. In the case of the AZT prodrugs, the AZT and peptide moieties were connected through an ester bond. To ensure a greater stability, particularly toward aminopeptidases, the N-terminal amino group of the peptide was masked by different protecting groups. In the case of the AZT-MP prodrugs, the various peptide moieties were connected via their N-terminal amino group to the AZT-phenoxy-phosphodiester group. We report also on (i) the stability of the peptide-AZT and peptide(AZT-MP) prodrugs when incubated in a physiological medium that does or does not contain 10% fetal calf serum, and in CEM cell lysates in order to mimic the behaviour of these compounds inside the cells, (ii) their ability to inhibit the HIV-PR activity and their susceptibility to be hydrolysed by PR, and (iii) their in vitro anti-HIV activities and cytotoxicities, which were evaluated in acutely-infected and uninfected MT4 and CEM cells, respectively. Moreover, their antiviral activities were also investigated in a thymidine kinase-deficient (TK- ) CEM cell line in order to gain further insight into their mechanism of action.

We report on the synthesis of a series of peptideAZT (2A, 2B, 5A, 5B) and peptide-(AZT-MP) conjugates incorporating peptide sequences found in a nonapeptide known to be a HIV-PR substrate. We also selected the AZT-MP phosphoramidate peptide-conjugates containing an additional alanine residue directly linked to the phosphorus atom. Indeed, among the various aminoacid phosphoramidates of ddN analogues known so far, the alanine derivative was shown to be one of the most efficient ddN-MP delivery system. All these conjugates contain the scissile Phe-Pro motif. In the case of the AZT prodrugs, the AZT and peptide moieties were connected through an ester bond. To ensure a greater stability, particularly toward aminopeptidases, the N-terminal amino group of the peptide was masked by different protecting groups. In the case of the AZT-MP prodrugs, the various peptide moieties were connected via their N-terminal amino group to the AZT-phenoxy-phosphodiester group. We report also on (i) the stability of the peptide-AZT and peptide(AZT-MP) prodrugs when incubated in a physiological medium that does or does not contain 10% fetal calf serum, and in CEM cell lysates in order to mimic the behaviour of these compounds inside the cells, (ii) their ability to inhibit the HIV-PR activity and their susceptibility to be hydrolysed by PR, and (iii) their in vitro anti-HIV activities and cytotoxicities, which were evaluated in acutely-infected and uninfected MT4 and CEM cells, respectively. Moreover, their antiviral activities were also investigated in a thymidine kinase-deficient (TK- ) CEM cell line in order to gain further insight into their mechanism of action.

We report on the synthesis of a series of peptideAZT (2A, 2B, 5A, 5B) and peptide-(AZT-MP) conjugates incorporating peptide sequences found in a nonapeptide known to be a HIV-PR substrate. We also selected the AZT-MP phosphoramidate peptide-conjugates containing an additional alanine residue directly linked to the phosphorus atom. Indeed, among the various aminoacid phosphoramidates of ddN analogues known so far, the alanine derivative was shown to be one of the most efficient ddN-MP delivery system. All these conjugates contain the scissile Phe-Pro motif. In the case of the AZT prodrugs, the AZT and peptide moieties were connected through an ester bond. To ensure a greater stability, particularly toward aminopeptidases, the N-terminal amino group of the peptide was masked by different protecting groups. In the case of the AZT-MP prodrugs, the various peptide moieties were connected via their N-terminal amino group to the AZT-phenoxy-phosphodiester group. We report also on (i) the stability of the peptide-AZT and peptide(AZT-MP) prodrugs when incubated in a physiological medium that does or does not contain 10% fetal calf serum, and in CEM cell lysates in order to mimic the behaviour of these compounds inside the cells, (ii) their ability to inhibit the HIV-PR activity and their susceptibility to be hydrolysed by PR, and (iii) their in vitro anti-HIV activities and cytotoxicities, which were evaluated in acutely-infected and uninfected MT4 and CEM cells, respectively. Moreover, their antiviral activities were also investigated in a thymidine kinase-deficient (TK- ) CEM cell line in order to gain further insight into their mechanism of action.

We report on the synthesis of a series of peptideAZT (2A, 2B, 5A, 5B) and peptide-(AZT-MP) conjugates incorporating peptide sequences found in a nonapeptide known to be a HIV-PR substrate. We also selected the AZT-MP phosphoramidate peptide-conjugates containing an additional alanine residue directly linked to the phosphorus atom. Indeed, among the various aminoacid phosphoramidates of ddN analogues known so far, the alanine derivative was shown to be one of the most efficient ddN-MP delivery system. All these conjugates contain the scissile Phe-Pro motif. In the case of the AZT prodrugs, the AZT and peptide moieties were connected through an ester bond. To ensure a greater stability, particularly toward aminopeptidases, the N-terminal amino group of the peptide was masked by different protecting groups. In the case of the AZT-MP prodrugs, the various peptide moieties were connected via their N-terminal amino group to the AZT-phenoxy-phosphodiester group. We report also on (i) the stability of the peptide-AZT and peptide(AZT-MP) prodrugs when incubated in a physiological medium that does or does not contain 10% fetal calf serum, and in CEM cell lysates in order to mimic the behaviour of these compounds inside the cells, (ii) their ability to inhibit the HIV-PR activity and their susceptibility to be hydrolysed by PR, and (iii) their in vitro anti-HIV activities and cytotoxicities, which were evaluated in acutely-infected and uninfected MT4 and CEM cells, respectively. Moreover, their antiviral activities were also investigated in a thymidine kinase-deficient (TK- ) CEM cell line in order to gain further insight into their mechanism of action.

We report on the synthesis of a series of peptideAZT (2A, 2B, 5A, 5B) and peptide-(AZT-MP) conjugates incorporating peptide sequences found in a nonapeptide known to be a HIV-PR substrate. We also selected the AZT-MP phosphoramidate peptide-conjugates containing an additional alanine residue directly linked to the phosphorus atom. Indeed, among the various aminoacid phosphoramidates of ddN analogues known so far, the alanine derivative was shown to be one of the most efficient ddN-MP delivery system. All these conjugates contain the scissile Phe-Pro motif. In the case of the AZT prodrugs, the AZT and peptide moieties were connected through an ester bond. To ensure a greater stability, particularly toward aminopeptidases, the N-terminal amino group of the peptide was masked by different protecting groups. In the case of the AZT-MP prodrugs, the various peptide moieties were connected via their N-terminal amino group to the AZT-phenoxy-phosphodiester group. We report also on (i) the stability of the peptide-AZT and peptide(AZT-MP) prodrugs when incubated in a physiological medium that does or does not contain 10% fetal calf serum, and in CEM cell lysates in order to mimic the behaviour of these compounds inside the cells, (ii) their ability to inhibit the HIV-PR activity and their susceptibility to be hydrolysed by PR, and (iii) their in vitro anti-HIV activities and cytotoxicities, which were evaluated in acutely-infected and uninfected MT4 and CEM cells, respectively. Moreover, their antiviral activities were also investigated in a thymidine kinase-deficient (TK- ) CEM cell line in order to gain further insight into their mechanism of action.

We report on the synthesis of a series of peptideAZT (2A, 2B, 5A, 5B) and peptide-(AZT-MP) conjugates incorporating peptide sequences found in a nonapeptide known to be a HIV-PR substrate. We also selected the AZT-MP phosphoramidate peptide-conjugates containing an additional alanine residue directly linked to the phosphorus atom. Indeed, among the various aminoacid phosphoramidates of ddN analogues known so far, the alanine derivative was shown to be one of the most efficient ddN-MP delivery system. All these conjugates contain the scissile Phe-Pro motif. In the case of the AZT prodrugs, the AZT and peptide moieties were connected through an ester bond. To ensure a greater stability, particularly toward aminopeptidases, the N-terminal amino group of the peptide was masked by different protecting groups. In the case of the AZT-MP prodrugs, the various peptide moieties were connected via their N-terminal amino group to the AZT-phenoxy-phosphodiester group. We report also on (i) the stability of the peptide-AZT and peptide(AZT-MP) prodrugs when incubated in a physiological medium that does or does not contain 10% fetal calf serum, and in CEM cell lysates in order to mimic the behaviour of these compounds inside the cells, (ii) their ability to inhibit the HIV-PR activity and their susceptibility to be hydrolysed by PR, and (iii) their in vitro anti-HIV activities and cytotoxicities, which were evaluated in acutely-infected and uninfected MT4 and CEM cells, respectively. Moreover, their antiviral activities were also investigated in a thymidine kinase-deficient (TK- ) CEM cell line in order to gain further insight into their mechanism of action.

We report on the synthesis of a series of peptideAZT (2A, 2B, 5A, 5B) and peptide-(AZT-MP) conjugates incorporating peptide sequences found in a nonapeptide known to be a HIV-PR substrate. We also selected the AZT-MP phosphoramidate peptide-conjugates containing an additional alanine residue directly linked to the phosphorus atom. Indeed, among the various aminoacid phosphoramidates of ddN analogues known so far, the alanine derivative was shown to be one of the most efficient ddN-MP delivery system. All these conjugates contain the scissile Phe-Pro motif. In the case of the AZT prodrugs, the AZT and peptide moieties were connected through an ester bond. To ensure a greater stability, particularly toward aminopeptidases, the N-terminal amino group of the peptide was masked by different protecting groups. In the case of the AZT-MP prodrugs, the various peptide moieties were connected via their N-terminal amino group to the AZT-phenoxy-phosphodiester group. We report also on (i) the stability of the peptide-AZT and peptide(AZT-MP) prodrugs when incubated in a physiological medium that does or does not contain 10% fetal calf serum, and in CEM cell lysates in order to mimic the behaviour of these compounds inside the cells, (ii) their ability to inhibit the HIV-PR activity and their susceptibility to be hydrolysed by PR, and (iii) their in vitro anti-HIV activities and cytotoxicities, which were evaluated in acutely-infected and uninfected MT4 and CEM cells, respectively. Moreover, their antiviral activities were also investigated in a thymidine kinase-deficient (TK- ) CEM cell line in order to gain further insight into their mechanism of action.