D-LysAsnProTyr tetrapeptide: a novel B-cell stimulant and stabilized bursin mimetic

Vaccine. 2000 Mar 17;18(18):1886-92. doi: 10.1016/s0264-410x(99)00374-6.

Abstract

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.

MeSH terms

  • Animals
  • Asparagine / immunology
  • B-Lymphocyte Subsets / immunology*
  • Cells, Cultured
  • Female
  • Half-Life
  • Lymphocyte Activation / immunology*
  • Lysine / immunology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Mimicry*
  • Oligopeptides / chemistry*
  • Oligopeptides / immunology*
  • Oligopeptides / pharmacology
  • Proline / immunology
  • Spleen
  • Tyrosine / immunology

Substances

  • Oligopeptides
  • Tyrosine
  • bursopoietin
  • Asparagine
  • Proline
  • Lysine