metastin-10 [F13Y]

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: metastin-10 [F13Y]
• 英文别名: Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Tyr-NH₂；H-Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Tyr-NH2；H-Tyr-Asu-Trp-Asu-Ser-Phe-Gly-Leu-Arg-Tyr-NH2；rat kisspeptin-10；murine kisspeptin；Kisspeptin-10, rat；(2S)-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-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-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]-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]butanediamide
• 化学式: C₆₃H₈₃N₁₇O₁₅
• 分子量: 1318.46
• InChiKey: HVPGTDOCSYBNFC-INXYWQKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  95
• 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：
  558
• 氢给体数：
  19
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  Fmoc-甘氨酸 、 Fmoc-L-亮氨酸 、 Fmoc-L-苯丙氨酸 、 FMOC-O-叔丁基-L-丝氨酸 、 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 metastin-10 [F13Y]
  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

• KISS1R RECEPTOR AGONIST COMPOUNDS AND USE THEREOF FOR INDUCING OVULATION IN MAMMALS
  申请人：INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE

  公开号：US20150361138A1

  公开（公告）日：2015-12-17

  A KISS1R agonist peptide compound capable of inducing ovulation in a female mammal is provided. The compound is a pseudopeptide having the C-terminal sequence: -XaaΨ[Tz]Xaa2-Xaa3-Xaa4-NH 2 (SEQ ID NO: 3), where Ψ[Tz] represents a 1,4-disubstituted 1,2,3-triazole group replacing the peptide bond between the Xaa1 residue and the Xaa2 residue, Xaa1 is Gly or Ala, Xaa2 is Leu or an aliphatic α-aminoacyl analogue residue, Xaa3 is Arg, Arg(Me) or a positively charged α-aminoacyl analogue residue, and Xaa4 is Tyr, Phe, Trp or an α-aminoacyl analogue residue such as aryl alanine; or an analogue of the pseudopeptide in which the amide peptide bond between Xaa2 and Xaa3 and/or between Xaa3 and Xaa4 is replaced with an isosteric bond, or a salt thereof.

  提供了一种KISS1R激动剂肽化合物，能够诱导雌性哺乳动物排卵。该化合物是一个伪肽，具有C-末端序列：-XaaΨ[Tz]Xaa2-Xaa3-Xaa4-NH2（SEQ ID NO: 3），其中Ψ[Tz]代表1,4-二取代1,2,3-三唑基团替换Xaa1残基和Xaa2残基之间的肽键，Xaa1为Gly或Ala，Xaa2为Leu或脂肪族α-氨基酰类似物残基，Xaa3为Arg，Arg(Me)或带正电荷的α-氨基酰类似物残基，Xaa4为Tyr，Phe，Trp或类似芳基丙氨酸的α-氨基酰类似物残基；或替代Xaa2和Xaa3之间和/或Xaa3和Xaa4之间的酰胺肽键的等构键或其盐。
• US9884891B2
  申请人：——

  公开号：US9884891B2

  公开（公告）日：2018-02-06
• 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.