Synthesis of peptide analogues containing phosphonamidate methyl ester functionality: HIV-1 proteinase inhibitors possessing unique cell uptake properties.
Stereochemically defined and epimeric phosphonamidate methyl ester-containing peptide analogues were synthesised and were found to be moderate inhibitors of the HIV-1 proteinase. All of the analogues containing the phosphonamidate ester grouping showed a marked ability to enter cells, as highlighted by the approximate equivalence of the IC50 values for enzyme inhibition in solution and inhibition of HIV-1 replication in virus infected cells.
Camp
N P
NP
School of Chemistry, The University, St. Andrews, Fife, U.K.
Perrey
D A
DA
Kinchington
D
D
Hawkins
P C
PC
Gani
D
D
D000595:Amino Acid Sequence; D004952:Esters / Q000138:chemical synthesis; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D008969:Molecular Sequence Data; D015394:Molecular Structure; D063065:Organophosphonates / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014779:Virus Replication / Q000187:drug effects
D004952:Esters; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D010455:Peptides