Ac-Tyr-Asn-Trp-Asn-Ser-Phe-azaGly-Leu-Arg-Tyr-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: Ac-Tyr-Asn-Trp-Asn-Ser-Phe-azaGly-Leu-Arg-Tyr-NH2
• 英文别名: (2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-N-[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamoyl]hydrazinyl]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]butanediamide
• 化学式: C₆₄H₈₄N₁₈O₁₆
• 分子量: 1361.48
• InChiKey: ZTGYVJDCOVUOOB-ZTNWZYIDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  98
• 可旋转键数：
  38
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  571
• 氢给体数：
  21
• 氢受体数：
  17

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  Fmoc-L-色氨酸(Boc)-OH	3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester	143824-78-6	C31H30N2O6	526.589

反应信息

• 作为产物：
  描述：

  Fmoc-L-亮氨酸 、 9-芴基甲基肼基甲酸酯 、 Fmoc-L-苯丙氨酸 、 FMOC-O-叔丁基-L-丝氨酸 、 乙酸酐 、 Fmoc-O-叔丁基-L-酪氨酸 、 Fmoc-N-三苯甲基-L-天冬酰胺 、 Fmoc-L-色氨酸(Boc)-OH 、 Fmoc-Pbf-L-精氨酸 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 Ac-Tyr-Asn-Trp-Asn-Ser-Phe-azaGly-Leu-Arg-Tyr-NH2
  参考文献：
  名称：

  Rational Design of Triazololipopeptides Analogs of Kisspeptin Inducing a Long-Lasting Increase of Gonadotropins

  摘要：

  New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-resistant amide mimic and a serum albumin-binding motif, respectively. These triazololipopeptides are highly potent full agonists of KISS1R and are >100 selective over the closely related NPFF1R. When injected in ewes with a quiescent reproductive system, the best compound of our series induced a much prolonged increase of luteinizing hormone release compared to KP10 and increased follicle-stimulating hormone plasma concentration. Hence, this KISS1R agonist is a new valuable pharmacological tool to explore the potential of KP system in reproduction control. Furthermore, it represents the first step to develop drugs treating reproductive system disorders due to a reduced activity of the hypothalamo-pituitary-gonadal axis such as delayed puberty, hypothalamic amenorrhea, and hypogonadotropic hypogonadism.

  DOI：

  10.1021/jm5019675

文献信息

• Rational Design of Triazololipopeptides Analogs of Kisspeptin Inducing a Long-Lasting Increase of Gonadotropins
  作者：Massimiliano Beltramo、Vincent Robert、Mathieu Galibert、Jean-Baptiste Madinier、Philippe Marceau、Hugues Dardente、Caroline Decourt、Nicolas De Roux、Didier Lomet、Agnès F. Delmas、Alain Caraty、Vincent Aucagne

  DOI：10.1021/jm5019675

  日期：2015.4.23

  New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-resistant amide mimic and a serum albumin-binding motif, respectively. These triazololipopeptides are highly potent full agonists of KISS1R and are >100 selective over the closely related NPFF1R. When injected in ewes with a quiescent reproductive system, the best compound of our series induced a much prolonged increase of luteinizing hormone release compared to KP10 and increased follicle-stimulating hormone plasma concentration. Hence, this KISS1R agonist is a new valuable pharmacological tool to explore the potential of KP system in reproduction control. Furthermore, it represents the first step to develop drugs treating reproductive system disorders due to a reduced activity of the hypothalamo-pituitary-gonadal axis such as delayed puberty, hypothalamic amenorrhea, and hypogonadotropic hypogonadism.