D-LysAsnProTyr tetrapeptide: a novel B-cell stimulant and stabilized bursin mimetic.
The tetrapeptide I (D-lysine-L-asparaginyl-L-prolyl-L-tyrosine or D-LysAsnProTyr), and analogue sequences, were synthesized and evaluated for the ability to stimulate immune cell subsets. These sequences were selected based on their perceived ability to readily adopt a beta-turn structure. In vitro immunological assays revealed a robust stimulation of mitogen activated B-cell proliferation and a modest to significant stimulation of cytotoxic T lymphocytes (CTLs). Further, this in vitro stimulation of B-cells was accompanied by an in vivo expansion of B-cells in C57BL/6 mice, as demonstrated by immunophenotyping experiments. Interestingly, a conformational analysis of the low energy conformers of I and the endogenous B-cell stimulant bursin (LysHisGlyNH2) shows that these molecules can be superimposed. However, I displayed significantly enhanced physiological stability. For a number of reasons, I may be a particularly useful vaccine adjuvant.
Gagnon
L
L
BioChem. Pharma Inc., 275 Armand-Frappier Blvd., Laval, Canada.
DiMarco
M
M
Kirby
R
R
Zacharie
B
B
Penney
C L
CL
D000818:Animals; D001216:Asparagine / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006207:Half-Life; D008213:Lymphocyte Activation / Q000276:immunology*; D008239:Lysine / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D011392:Proline / Q000276:immunology; D013154:Spleen; D014443:Tyrosine / Q000276:immunology
D009842:Oligopeptides; D014443:Tyrosine; C016281:bursopoietin; D001216:Asparagine; D011392:Proline; D008239:Lysine