H-His-D-Trp-Ala-aza-Tyr-D-Phe-Lys-NH₂

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: H-His-D-Trp-Ala-aza-Tyr-D-Phe-Lys-NH₂
• 英文别名: (2S)-6-amino-2-[[(2R)-2-[[[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-[(4-hydroxyphenyl)methyl]carbamoyl]amino]-3-phenylpropanoyl]amino]hexanamide
• 化学式: C₄₃H₅₄N₁₂O₇
• 分子量: 850.978
• InChiKey: ULBKJPIZMQDQBL-MHKQCRJVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  62
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  309
• 氢给体数：
  11
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N'-(4-(tert-butyldimethylsilyloxy)benzyl)-fluorenylmethyl carbazate 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 3.25h， 生成 H-His-D-Trp-Ala-aza-Tyr-D-Phe-Lys-NH₂
  参考文献：
  名称：

  Azapeptide Analogues of the Growth Hormone Releasing Peptide 6 as Cluster of Differentiation 36 Receptor Ligands with Reduced Affinity for the Growth Hormone Secretagogue Receptor 1a

  摘要：

  The synthetic hexapeptide growth hormone releasing peptide-6 (GHRP-6) exhibits dual affinity for the growth hormone secretagogue receptor la (GHS-R1a) and the cluster of differentiation 36 (CD36) receptor. Azapeptide GHRP-6 analogues have been synthesized, exhibiting micromolar affinity to the CD36 receptor with reduced affinity toward the GHS-R1a. A combinatorial split-and-mix approach furnished aza-GHRP-6 leads, which were further examined by alanine scanning. Incorporation of an aza-amino acid residue respectively at the D-Trp(2) Ala(3), or Trp(4) position gave aza-GHRP-6 analogues with reduced affinity toward the GHS-R1a by at least a factor of 100 and in certain cases retained affinity for the CD36 receptor. In the latter cases, the D-Trp2 residue proved important for CD36 receptor affinity; however, His' could be replaced by Ala' without considerable loss of binding. In a microvascular sprouting assay using a choroid explant, [azaTyr(4)]-GHRP-6 (15), [Ala(1), azaPhe(2)]-GHRP-6 (16), and [azaLeu(3), Ala(6)]-GHRP-6 (33) all exhibited antiangiogenic activity.

  DOI：

  10.1021/jm300557t

文献信息

• AZAPEPTIDES AS CD36 BINDING COMPOUNDS
  申请人：Ong Huy

  公开号：US20100210566A1

  公开（公告）日：2010-08-19

  An azapeptide derivative of growth hormone releasing peptide (GHRP) of Formula I: A-(Xaa) a -N(R A )—N(R B )—C(O)-(Xaa′) b -B which binds to CD 36.

  一种与CD36结合的生长激素释放肽（GHRP）的azapeptide衍生物，化学式为：A-（Xaa）a-N（RA）-N（RB）-C（O）-（Xaa'）b-B。
• US8435954B2
  申请人：——

  公开号：US8435954B2

  公开（公告）日：2013-05-07
• US9115171B2
  申请人：——

  公开号：US9115171B2

  公开（公告）日：2015-08-25
• US9708370B2
  申请人：——

  公开号：US9708370B2

  公开（公告）日：2017-07-18
• Azapeptide Analogues of the Growth Hormone Releasing Peptide 6 as Cluster of Differentiation 36 Receptor Ligands with Reduced Affinity for the Growth Hormone Secretagogue Receptor 1a
  作者：Caroline Proulx、Émilie Picard、Damien Boeglin、Petra Pohankova、Sylvain Chemtob、Huy Ong、William D. Lubell

  DOI：10.1021/jm300557t

  日期：2012.7.26

  The synthetic hexapeptide growth hormone releasing peptide-6 (GHRP-6) exhibits dual affinity for the growth hormone secretagogue receptor la (GHS-R1a) and the cluster of differentiation 36 (CD36) receptor. Azapeptide GHRP-6 analogues have been synthesized, exhibiting micromolar affinity to the CD36 receptor with reduced affinity toward the GHS-R1a. A combinatorial split-and-mix approach furnished aza-GHRP-6 leads, which were further examined by alanine scanning. Incorporation of an aza-amino acid residue respectively at the D-Trp(2) Ala(3), or Trp(4) position gave aza-GHRP-6 analogues with reduced affinity toward the GHS-R1a by at least a factor of 100 and in certain cases retained affinity for the CD36 receptor. In the latter cases, the D-Trp2 residue proved important for CD36 receptor affinity; however, His' could be replaced by Ala' without considerable loss of binding. In a microvascular sprouting assay using a choroid explant, [azaTyr(4)]-GHRP-6 (15), [Ala(1), azaPhe(2)]-GHRP-6 (16), and [azaLeu(3), Ala(6)]-GHRP-6 (33) all exhibited antiangiogenic activity.