Improved enzymatic synthesis of a highly potent oligosaccharide antagonist of L-selectin

• Published in: FEBS letters Vol. 419; no. 2; pp. 220 - 226
• Main Authors: Salminen, Heidi, Ahokas, Katja, Niemelä, Ritva, Penttilä, Leena, Maaheimo, Hannu, Helin, Jari, Costello, Catherine E, Renkonen, Ossi
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15-12-1997
• Subjects: Animals; Carbohydrate Sequence; d-galactose; Enzymatic synthesis; Fuc; Gal; GlcNAc; HexNAc; high pH anion exchange chromatography; HPAEC; l-fucose; L-Selectin - drug effects; L-Selectin antagonist; LacNAc; MALDI-TOF-MS; maltoheptaose; maltopentaose; matrix-assisted laser desorption/ionization mass spectrometry with time-of-flight detection; Midchain β1,6-GlcNAc transferase; Molecular Sequence Data; N-acetyl-d-glucosamine; N-acetyl-d-glucosamine or N-acetyl-d-mannosamine; N-acetyl-neuraminic acid; N-acetyllactosamine or Galβ1–4GlcNAc; Neu5Ac; NMR; nuclear magnetic resonance; Oligosaccharides - chemical synthesis; Oligosaccharides - pharmacology; PAD; pulsed amperometric detection; Rats; sialyl Lewis x or Neu5Acα2–3Galβ1–4(Fucα1–3)GlcNAc; sLex; Tetravalent sLex glycan; Enzymatic synthesis; MALDI-TOF-MS; MP; Neu5Ac; HPAEC; L-Selectin antagonist; Midchain β1,6-GlcNAc transferase; NMR; PAD; Gal; Fuc; Tetravalent sLex glycan; HexNAc; LacNAc; sLex; GlcNAc; MH
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(97)01462-2

The polylactosamine sLexβ1–3′(sLexβ1–6′)LacNAcβ1–3′(sLexβ1–6′)LacNAcβ1–3′(sLexβ1–6′)LacNAc (
7) (where sLex is Neu5Acα2–3Galβ1–4(Fucα1–3)GlcNAc and LacNAc is Galβ1–4GlcNAc) is a nanomolar L-selectin antagonist and therefore a potential anti-inflammatory agent (Renkonen et al. (1997) Glycobiology, 7, 453). Here we describe an improved synthesis of
7. The octasaccharide LacNAcβ1–3′LacNAcβ1–3′LacNAcβ1–3′LacNAc (
4) was converted into the triply branched undecasaccharide LacNAcβ1–3′(GlcNAcβ1–6′)LacNAcβ1–3′(GlcNAcβ1–6′)LacNAcβ1–3′(GlcNAcβ1–6′)LacNAc (
5) by incubation with UDP-GlcNAc and the midchain β1,6-GlcNAc transferase activity of rat serum. Glycan
5 was enzymatically β1,4-galactosylated to LacNAcβ1–3′(LacNAcβ1–6′)LacNAcβ1–3′(LacNAcβ1–6′)LacNAcβ1–3′(LacNAcβ1–6′)LacNAc (
6). Combined with the enzymatic conversion of
6 to
7 (Renkonen et al., loc. cit.) and the available chemical synthesis of
4, our data improve the availability of
7 for full assessment of its anti-inflammatory properties.