Glyco-replica Peptides Which Mimic Glycosphingolipids |
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In 1990, Scott and Smith reported the construction of a phage-displayed
peptide library in which a randomly arranged hexamer peptide
is expressed on a surface protein (pIII) of the phage (1). This
library was first developed for the selection of peptides which
are recognized by a monoclonal antibody or a receptor. We applied
the phage peptide library technique to the preparation of peptides
which mimic non-peptide molecules such as glycosphingolipids
(2,3). This work is based on the molecular mimicry hypothesis
that peptides recognized by an antibody against glycosphingolipid
can mimic the structure of the antigen. We named these oligosaccharide-mimicking
peptides "glyco-replica peptides" (2). Westerink et al. (4) selected a tripeptide, YRY (Tyr-Arg-Tyr), by the phage peptide library and a monoclonal antibody against alpha2-9 sialic acid linkage of meningococcal group C capsular polysaccharide. The peptide was found to mimic not only the alpha2-9 sialic acid linkage but also Fuc alpha1-3GlcNAc of LeY. The anti-YRY antiserum obtained by immunization with the peptide cross-reacted with both LeY and envelope glycoprotein (gp120) of HIV. Furthermore, they found that HIV infection was suppressed by the anti-YRY antiserum, indicating that glyco-replica peptides are useful tools for adjuvant therapy against infectious diseases and cancer. Recently, we found that a disialoganglioside GD1a expressed on cell surface of murine lymphosarcoma cell line, RAW117-H10, which has a high metastatic tendency for the liver, is involved in the adhesion between RAW117-H10 and hepatic sinusoidal endothelial (HSE) cells. GD1a-replica peptides obtained from a phage peptide library inhibited both the adhesion of RAW117-H10 cells to HSE cells in vitro and metastasis of the tumor cells to the liver, spleen, and lung in vivo (3). In other cases, we found that paragloboside (nLc4Cer)-replica peptides have a binding property to Ricinus communis lectin and regulate beta-galactosidase activity when paragloboside is used as the substrate. Since the glyco-replica peptides prepared by the present method are shown to mimic the functional roles of the oligosaccharides, the phage displayed peptide library will be used more widely in the research field of glycoconjugates. |
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| Dai Ishikawa and Takao Taki (Cellular Technology Institute. Otsuka Pharmaceutical Co., Ltd.) | |||||||||||||||||
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| Mar.15, 1999 | |||||||||||||||||
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