Peptide sugar mimetics prevent HIV type 1 replication in peripheral blood mononuclear cells in the presence of HIV-positive antiserum.
Cells of the immune system express a number of receptors that bind carbohydrate ligands. We questioned whether peptide mimetics of these ligands will activate phagocytic cells and thereby enhance an antiviral response. Short peptide sequences were identified by computational modeling of docking to glycan-specific lectins, selected as receptor analogs, and incorporated into quadravalent structures by peptide synthesis. A peptide with the sequence HPSLK bound to several lectins specific for monosaccharides and to lectins specific for Neu5Ac-Gal-containing complex glycans, whereas a longer sequence, NPSHPLSG, bound only lectins specific for the more complex glycans. In cultures of peripheral blood mononuclear cells (PBMCs) these peptides stimulated phagocytosis of opsonized microspheres. The peptides inhibited replication of HIV-1 in PBMC cultures by 20-80% at concentrations between 1 nM and 1 muM but inhibited replication 100% in the presence of diluted HIV-positive antiserum that alone inhibited replication by 30%. HPSLK caused about 50% loss of viability of cells at 1 mM, a concentration 10(6)-fold higher than an effective inhibitory concentration, but no toxicity was observed with NPSHPLSG. These results demonstrated that peptidomimetics of glycan ligands of cellular receptors are effective in activating phagocytosis, which may be a factor in providing complete inhibition of HIV-1 replication in vitro.
Susavion Biosciences, Inc., Tempe, AZ 85281, USA.
Laura L
LL
Eggink
Maria
M
Salas
Carl V
CV
Hanson
J Kenneth
JK
Hoober
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000633:toxicity; D032701:Biomimetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D010455:Peptides / Q000494:pharmacology* / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D010455:Peptides