A synthetic peptidemimetic substrate of the human immunodeficiency virus 1 (HIV-1) protease with a nonhydrolyzable pseudodipeptidyl insert at the protease cleavage site was prepared. The peptide U-81749 inhibited recombinant HIV-1 protease in vitro (inhibition constant Ki of 70 nanomolar) and HIV-1 replication in human peripheral blood lymphocytes (inhibitory concentration IC50 of 0.1 to 1 micromolar). Moreover, 10 micromolar concentrations of U-81749 significantly inhibited proteolysis of the HIV-1 gag polyprotein (p55) to the mature viral structural proteins p24 and p17 in cells infected with a recombinant vaccinia virus expressing the HIV-1 gag-pol genes. The HIV-1 like particles released from inhibitor-treated cells contained almost exclusively p55 and other gag precursors, but not p24. Incubation of HIV-like particles recovered from drug-treated cultures in drug-free medium indicated that inhibition of p55 proteolysis was at least partially reversible, suggesting that U-81749 was present within the particles.

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We report on characterization of a 170,000 Da glycoprotein found exclusively in the PNS. We refer to this protein as the Schwann cell membrane glycoprotein (SAG). SAG contains the HNK-1 carbohydrate, which is considered by some to be a marker of adhesion molecules. Its N-terminal sequence is not similar to previously known polypeptide sequences. SAG is found exclusively in the PNS, is present in rat sciatic nerve prior to myelination, and is in both myelinating and nonmyelinating Schwann cells. Tumors of Schwann cell lineage express SAG where axons are present (neurofibromas) but do not in the absence of axons (schwannomas). Schwannoma cells in culture do not express SAG even when exposed to forskolin, an activator of adenylate cyclase. However, schwannoma cells grown in the presence of a neuronal cell line (PC12) express SAG.