2-azidoethyl-O-(5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylic acid)-(2→6)-O-β-D-galactopyranosyl-(1→4)-O-β-D-glucopyranoside

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-azidoethyl-O-(5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylic acid)-(2→6)-O-β-D-galactopyranosyl-(1→4)-O-β-D-glucopyranoside
• 英文别名: (2R,4S,5R,6R)-5-acetamido-2-[[(2R,3R,4S,5R,6S)-6-[(2R,3S,4R,5R,6R)-6-(2-azidoethoxy)-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid
• 化学式: C₂₅H₄₂N₄O₁₉
• 分子量: 702.624
• InChiKey: JXYCIVQUWDTCRC-FRFUNZCYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.3
• 重原子数：
  48
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  338
• 氢给体数：
  12
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  N-[2-(2-(2-(2-Propynyloxy)ethoxy)ethoxy)ethyl]maleimide 、 2-azidoethyl-O-(5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylic acid)-(2→6)-O-β-D-galactopyranosyl-(1→4)-O-β-D-glucopyranoside 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.0h， 以70%的产率得到N-[2-(2-(2-((1-(O-(5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2→6)-O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyloxyethyl)-1H-1,2,3-triazol-4-yl)methoxy)ethoxy)ethoxy)ethyl]maleimide
  参考文献：
  名称：

  Glycosylated Enfuvirtide: A Long-Lasting Glycopeptide with Potent Anti-HIV Activity

  摘要：

  Many peptide-based therapeutics have short circulatory half-lives. We report here that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be dramatically improved by a chemical glycosylation approach. A set of glycosylated ENFs with varying glycosylation sites and glycan structures were synthesized. Among these, a sialic acid-introduced peptide (SL-ENF) demonstrated a 15-fold extended half-life in rats relative to ENF (T-1/2: 23.1 vs 1.5 h), and its antiviral potency was comparable to that of ENF (EC50: 2 vs 3 nM). SL-ENF bound to a functional fragment of the HIV fusogenic protein gp41 and formed complexes with high affinity and a-helicity, revealing the mechanism behind its potent antiviral activity. Because it is widely accepted in biology that glycosylation protects proteins from denaturation and proteases, our approach may be useful for the development of novel protein and peptide drugs with enhanced pharmaceutical properties.

  DOI：

  10.1021/jm5016582
• 作为产物：
  描述：

  N-乙酰神经氨酸水合物 、 2-azidoethyl β-D-galactopyranosyl-(1->4)-β-D-glucopyranoside 在 α2,6-sialyltransferase 作用下， 以 aq. buffer 为溶剂， 反应 6.0h， 以85%的产率得到2-azidoethyl-O-(5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylic acid)-(2→6)-O-β-D-galactopyranosyl-(1→4)-O-β-D-glucopyranoside
  参考文献：
  名称：

  Glycosylated Enfuvirtide: A Long-Lasting Glycopeptide with Potent Anti-HIV Activity

  摘要：

  Many peptide-based therapeutics have short circulatory half-lives. We report here that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be dramatically improved by a chemical glycosylation approach. A set of glycosylated ENFs with varying glycosylation sites and glycan structures were synthesized. Among these, a sialic acid-introduced peptide (SL-ENF) demonstrated a 15-fold extended half-life in rats relative to ENF (T-1/2: 23.1 vs 1.5 h), and its antiviral potency was comparable to that of ENF (EC50: 2 vs 3 nM). SL-ENF bound to a functional fragment of the HIV fusogenic protein gp41 and formed complexes with high affinity and a-helicity, revealing the mechanism behind its potent antiviral activity. Because it is widely accepted in biology that glycosylation protects proteins from denaturation and proteases, our approach may be useful for the development of novel protein and peptide drugs with enhanced pharmaceutical properties.

  DOI：

  10.1021/jm5016582

文献信息

• Glycosylated Enfuvirtide: A Long-Lasting Glycopeptide with Potent Anti-HIV Activity
  作者：Shuihong Cheng、Xuesong Chang、Yan Wang、George F. Gao、Yiming Shao、Liying Ma、Xuebing Li

  DOI：10.1021/jm5016582

  日期：2015.2.12

  Many peptide-based therapeutics have short circulatory half-lives. We report here that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be dramatically improved by a chemical glycosylation approach. A set of glycosylated ENFs with varying glycosylation sites and glycan structures were synthesized. Among these, a sialic acid-introduced peptide (SL-ENF) demonstrated a 15-fold extended half-life in rats relative to ENF (T-1/2: 23.1 vs 1.5 h), and its antiviral potency was comparable to that of ENF (EC50: 2 vs 3 nM). SL-ENF bound to a functional fragment of the HIV fusogenic protein gp41 and formed complexes with high affinity and a-helicity, revealing the mechanism behind its potent antiviral activity. Because it is widely accepted in biology that glycosylation protects proteins from denaturation and proteases, our approach may be useful for the development of novel protein and peptide drugs with enhanced pharmaceutical properties.