Synthesis of C-terminal glycopeptides from resin-bound glycosyl azides via a modified Staudinger reaction

被引:70
作者
Malkinson, JP
Falconer, RA
Toth, I
机构
[1] Univ London, Sch Pharm, Dept Pharmaceut & Biol Chem, London WC1N 1AX, England
[2] Univ Queensland, Sch Pharm, Brisbane, Qld 4072, Australia
关键词
D O I
10.1021/jo000381z
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The solid-phase synthesis of glycopeptides containing the sugar at the C-terminus is reported. The method is demonstrated on a model, the endogenous antinociceptive peptide Leu-enkephalin. 2,3,4- Tri-O-acetyl-1-azido-1-deoxy-beta-D-glucopyranuronic acid was synthesized and immobilized onto a variety of derivatized resins. Conjugation of the first amino acid was accomplished by reaction of the resin-bound glycosyl azide with an activated amino acid, in one step, via a modified Staudinger reaction. Standard solid-phase peptide synthesis then resulted in the desired amide-linked glycopeptide. Reaction conditions and reagents for the glycosylation were varied to optimize the yield and purity of the product. The optimum conditions were found to be the use of a 4-fold molar excess of activated amino acid and 3-fold excess of tri-n-butylphosphine in tetrahydrofuran. This methodology is generally applicable to most peptide sequences and is compatible with both Bocand Fmoc- synthetic strategies on a variety of resins.
引用
收藏
页码:5249 / 5252
页数:4
相关论文
共 14 条
  • [1] BAYLEY H, 1989, TETRAHEDRON LETT, V30, P1927
  • [2] BLITHE DL, 1993, TRENDS GLYCOSCI GLYC, V5, P81
  • [3] Novel liposaccharide conjugates for drug and peptide delivery
    Drouillat, B
    Hillery, AM
    Dekany, G
    Falconer, R
    Wright, K
    Toth, I
    [J]. JOURNAL OF PHARMACEUTICAL SCIENCES, 1998, 87 (01) : 25 - 30
  • [4] Solid phase synthesis of C-terminal carbohydrate modified enkephalins
    Drouillat, B
    Kellam, B
    Dekany, G
    Starr, MS
    Toth, I
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (17) : 2247 - 2250
  • [5] SYNTHETIC N-GLYGOSYL AND O-GLYCOSYL DERIVATIVES OF L-ASPARAGINE, L-SERINE, AND L-THREONINE
    GARG, HG
    JEANLOZ, RW
    [J]. ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, 1985, 43 : 135 - 201
  • [6] RECENT ADVANCES IN THE STAUDINGER REACTION
    GOLOLOBOV, YG
    KASUKHIN, LF
    [J]. TETRAHEDRON, 1992, 48 (08) : 1353 - 1406
  • [7] IDENTIFICATION OF 2 RELATED PENTAPEPTIDES FROM BRAIN WITH POTENT OPIATE AGONIST ACTIVITY
    HUGHES, J
    SMITH, TW
    KOSTERLITZ, HW
    FOTHERGILL, LA
    MORGAN, BA
    MORRIS, HR
    [J]. NATURE, 1975, 258 (5536) : 577 - 579
  • [8] INAZU T, 1993, SYNLETT, P869
  • [9] COLOR TEST FOR DETECTION OF FREE TERMINAL AMINO GROUPS IN SOLID-PHASE SYNTHESIS OF PEPTIDES
    KAISER, E
    COLESCOT.RL
    BOSSINGE.CD
    COOK, PI
    [J]. ANALYTICAL BIOCHEMISTRY, 1970, 34 (02) : 595 - &
  • [10] Synthesis and in vitro evaluation of lipoamino acid and carbohydrate-modified enkephalins as potential antinociceptive agents
    Kellam, B
    Drouillat, B
    Dekany, G
    Starr, MS
    Toth, I
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1998, 161 (01) : 55 - 64