Peptide Sugar Mimetics Prevent HIV Type 1 Replication in Peripheral Blood Mononuclear Cells in the Presence of HIV-Positive Antiserum

Abstract

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.

Peptide Mimetics of Terminal Sugars of Complex Glycans

“…Nanomolar concentrations of the peptides stimulated uptake of opsonized microspheres by adherent cells in cultures of human peripheral blood mononuclear cells (PBMCs). 8 The data reported here extend our previous studies on the mimetic character of these peptides.…”

“…Phagocytic activity was assayed as described previously. 8 Briefly, streptavidin-coated microspheres, dyed with Dragon Green (0.97 µm diameter, Bangs Laboratories, Inc., Fishers, IN), were opsonized with rabbit anti-streptavidin serum (Sigma-Aldrich) and washed with phosphate buffered saline, pH 7.4 (PBS). Human PBMCs were cultured in microtiter plates in RPMI-1640 medium containing 10% fetal bovine serum (FBS) and 1:100 dilution of penicillin-streptomycin solution (Mediatech, Inc., Herndon, VA).…”

“…23 Correspondence between predicted binding energy and extent of binding to these lectins was observed for this peptide. 8 We chose the lectins from Triticus vulgaris (wheat germ agglutinin, WGA) and from Dolichos biflorus (DB) for further study because modeling predicted that both lectins should bind this peptide with a relatively high binding energy.…”

“…6 We previously identified several short peptide sequences by molecular modeling, which were incorporated into multivalent structures that bound to several lectins with high affinity. 7,8 Multivalency of ligands is required for high affinity interactions [9][10][11] and to facilitate cross-linking of receptors, which is often required for activation of cellular responses. 12 Well-characterized lectins were used as receptor analogs in our study to analyze the mimetic properties of peptides.…”

Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part 1: stimulatory effects on blood monocytes and monocyte-derived cells of the brain

“…In this study, we investigated the effects of the activation of GCLRs in stimulating anti-glioma immunity based on previous work7,8 conducted with these receptors. We sought to determine whether such activation influenced monocytic activity in cancers and other immune-related diseases, and to determine whether there was potential for use of such treatments against a malignant glioma.…”