c[CO-2,6-pyridine-CO-D-Phe-Arg-Trp-Lys]-NH2 | 1004752-74-2

• 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: c[CO-2,6-pyridine-CO-D-Phe-Arg-Trp-Lys]-NH2
• 英文别名: (4R,7S,10S,13S)-4-benzyl-7-[3-(diaminomethylideneamino)propyl]-10-(1H-indol-3-ylmethyl)-2,5,8,11,19-pentaoxo-3,6,9,12,18,24-hexazabicyclo[18.3.1]tetracosa-1(23),20(24),21-triene-13-carboxamide
• CAS: 1004752-74-2
• 化学式: C₃₉H₄₇N₁₁O₆
• 分子量: 765.872
• InChiKey: PRDKVDXHWLLADO-ZKKLFSJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  56
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  282
• 氢给体数：
  9
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  吡啶-2,6-二甲酸 、 Fmoc-D-苯丙氨酸 、 N-[(9H-芴-9-甲氧基)羰基]-N'-[(2-丙烯氧基)羰基]-L-赖氨酸 、 Fmoc-Pbf-L-精氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 c[CO-2,6-pyridine-CO-D-Phe-Arg-Trp-Lys]-NH2
  参考文献：
  名称：

  Structure–Activity Relationships of Cyclic Lactam Analogues of α-Melanocyte-Stimulating Hormone (α-MSH) Targeting the Human Melanocortin-3 Receptor

  摘要：

  A variety of dicarboxylic acid linkers introduced between the a-amino group of Pro(6) and the C-ammo group of Lys(10) of the cyclic lactam a-melanocyte-stimulating hormone (alpha-MSH)-derived Pro(6) -D-Phe(7)/D-Nal(2')(7)- Arg(8)-Trp(9)-Lys(10)-NH2 pentapeptide template lead to nanomolar range and selective hMC3R agonists and antagonists'. Replacement of the Pro residue and the dicarboxylic acid linker with 2,3-pyrazine-dicarboxylic acid furnished a highly selective nanomolar range hMC3R partial agonist (analogue 12, c[CO-2,3-pyrazine-CO-D-Phe-Arg-Trp-Lys]-NH2, EC50 = 27 nM, 70% max cAMP) and an hMC3R antagonist (analogue 13, c[CO-2,3-pyrazine-CO-D-Nal(2')-Arg-Trp-Lys]-NH2, IC50 = 23 nM). Modeling experiments suggest that 2,3-pyrazinedicarboxylic acid stabilizes a beta-turn-like structure with the D-Phe/D-Nal(2') residues, which explains the high potency of the corresponding peptides. Placement of a Nle residue in position 6 produced a hMC3R/hMC5R antagonist (analogue 15, c[CO-(CH2)(2)-CO-Nle-D-Nal(2')-Arg-Trp-Lys]-NH2, IC50 = 12 and 17 nM, respectively), similarly to the previously described cyclic gamma-melanocyte-stimulating hormone (gamma-MSH)-derived hMC3R/hMC5R antagonists. These newly developed melanotropins will serve as critical biochemical tools for elucidating the full spectrum of functions performed by the physiologically important melanocortin-3. receptor.

  DOI：

  10.1021/jm070461w

文献信息

• Structure–Activity Relationships of Cyclic Lactam Analogues of α-Melanocyte-Stimulating Hormone (α-MSH) Targeting the Human Melanocortin-3 Receptor
  作者：Alexander V. Mayorov、Minying Cai、Erin S. Palmer、Matthew M. Dedek、James P. Cain、April R. Van Scoy、Bahar Tan、Josef Vagner、Dev Trivedi、Victor J. Hruby

  DOI：10.1021/jm070461w

  日期：2008.1.1

  A variety of dicarboxylic acid linkers introduced between the a-amino group of Pro(6) and the C-ammo group of Lys(10) of the cyclic lactam a-melanocyte-stimulating hormone (alpha-MSH)-derived Pro(6) -D-Phe(7)/D-Nal(2')(7)- Arg(8)-Trp(9)-Lys(10)-NH2 pentapeptide template lead to nanomolar range and selective hMC3R agonists and antagonists'. Replacement of the Pro residue and the dicarboxylic acid linker with 2,3-pyrazine-dicarboxylic acid furnished a highly selective nanomolar range hMC3R partial agonist (analogue 12, c[CO-2,3-pyrazine-CO-D-Phe-Arg-Trp-Lys]-NH2, EC50 = 27 nM, 70% max cAMP) and an hMC3R antagonist (analogue 13, c[CO-2,3-pyrazine-CO-D-Nal(2')-Arg-Trp-Lys]-NH2, IC50 = 23 nM). Modeling experiments suggest that 2,3-pyrazinedicarboxylic acid stabilizes a beta-turn-like structure with the D-Phe/D-Nal(2') residues, which explains the high potency of the corresponding peptides. Placement of a Nle residue in position 6 produced a hMC3R/hMC5R antagonist (analogue 15, c[CO-(CH2)(2)-CO-Nle-D-Nal(2')-Arg-Trp-Lys]-NH2, IC50 = 12 and 17 nM, respectively), similarly to the previously described cyclic gamma-melanocyte-stimulating hormone (gamma-MSH)-derived hMC3R/hMC5R antagonists. These newly developed melanotropins will serve as critical biochemical tools for elucidating the full spectrum of functions performed by the physiologically important melanocortin-3. receptor.