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Improved enzymatic synthesis of a highly potent oligosaccharide antagonist of L‐selectin
Author(s) -
Salminen Heidi,
Ahokas Katja,
Niemelä Ritva,
Penttilä Leena,
Maaheimo Hannu,
Helin Jari,
Costello Catherine E,
Renkonen Ossi
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01462-2
Subject(s) - chemistry , glycan , biochemistry , glycoprotein
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.