Ac-Nle-c[Asp-His-Phe-Arg-Trp-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: Ac-Nle-c[Asp-His-Phe-Arg-Trp-Lys]-NH₂
• 英文别名: Ac-Nle-c(Asp-His-Phe-Arg-Trp-Lys)-NH2；Melanotan II Acetic Acid Salt；(3S,6S,9S,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide
• 化学式: C₅₀H₆₉N₁₅O₉
• 分子量: 1024.19
• InChiKey: JDKLPDJLXHXHNV-IFLLZMBLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  74
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  385
• 氢给体数：
  13
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  BOC-L-苯丙氨酸 、 N-叔丁氧羰基-N'-甲苯磺酰基-L-精氨酸 、 NAlpha-BOC-Nε-FMOC-L-赖氨酸 、 Boc-Trp(Mts)-OH 、 alkaline earth salt of/the/ methylsulfuric acid 生成 Ac-Nle-c[Asp-His-Phe-Arg-Trp-Lys]-NH₂
  参考文献：
  名称：

  β-Methylation of the Phe⁷ and Trp⁹ Melanotropin Side Chain Pharmacophores Affects Ligand−Receptor Interactions and Prolonged Biological Activity

  摘要：

  Topographically modified melanotropin side chain pharmacophore residues Phe(7) and Trp(9) in a cyclic peptide template (Ac-Nle(4)-c[Asp-His-Xaa(7)-Arg-Yaa(9)-Lys]-NH2) and Phe(7) in a linear peptide template (Ac-Ser-Tyr-Ser-Nle(4)-Glu-His-Xaa(7)-Arg-Trp-Gly-Lys-Pro-Val-NH2) result in differences in potency and prolonged biological activity in the frog and lizard skin bioassays. These topographic modifications included the four isomers of beta-methylphenylalanine (beta-MePhe)(7) and beta-methyltryptophan (beta-MeTrp)(9) and the two isomers of 1,2,3,4-tetrahydro-beta-carboline (Tea)(9) Modifications in the cyclic template resulted in up to a 1000-fold difference in potency for the beta-MePhe(7) stereoisomeric peptides; up to a 476-fold difference in potency resulted for the beta-MeTrp(9) peptides, and about a 50-fold difference between the Tca(9)-containing peptides. Up to a 40-fold difference in potency resulted for the beta-MePhe(7)? stereoisomeric peptides using the linear template in these assays. The relative potency racing for modifications in the cyclic template of beta-MePhe(7) were 2R,3S > 2S,3S = 2S,3R 2 > 2R,3R in the frog assay and 2S,3R > 2R,3S > 2S,3S > 2R,3R in the lizard assay. The relative potencies for modifications in the cyclic template of beta-MeTrp(9) were 2R,3S > 2R,3R > 2S,3R > 2S,3R in the frog assay and 2S,3S = 2R,3R > 2R,3S > 2S,3R in the lizard assay. The relative potencies for modifications in the cyclic template of Tca(9) were DTca > LTca in both assays, Significant differences in prolonged (residual) activities were also observed for these modified peptides and were dependent upon stereochemistry of the beta-methyl amino acid, peptide template, and bioassay system. Furthermore, comparisons of beta-MeTrp(9) stereoisomeric peptides on the frog, lizard, and human MC1 receptors suggest that structure-activity relationships on both the classical frog and lizard skin bioassays do not necessarily predict corresponding SAR profiles for the human melanocortin receptors, indicating a remarkable species specificity of the MC1 receptor requirements.

  DOI：

  10.1021/jm970018t

文献信息

• A Tetrazine-Labile Vinyl Ether Benzyloxycarbonyl Protecting Group (VeZ): An Orthogonal Tool for Solid-Phase Peptide Chemistry
  作者：Matteo Staderini、Alessia Gambardella、Annamaria Lilienkampf、Mark Bradley

  DOI：10.1021/acs.orglett.8b00898

  日期：2018.6.1

  selectively cleaved by treatment with tetrazines via an inverse electron-demand Diels–Alder reaction. This represents a new orthogonal protecting group for solid-phase peptide synthesis, with Fmoc-Lys(VeZ)-OH as a versatile alternative to Fmoc-Lys(Alloc)-OH and Fmoc-Lys(Dde)-OH, as demonstrated by the synthesis of two biologically relevant cyclic peptides.

  乙烯基醚苄氧基羰基（VeZ）保护基可通过反电子需求的Diels-Alder反应用四嗪处理选择性地裂解。这代表了固相肽合成的一个新的正交保护基，Fmoc-Lys（VeZ）-OH是Fmoc-Lys（Alloc）-OH和Fmoc-Lys（Dde）-OH的多用途替代品，合成两个生物学上相关的环肽。
• 2D green SPPS: green solvents for on-resin removal of acid sensitive protecting groups and lactamization
  作者：Jan Pawlas、Biljana Antonic、Marika Lundqvist、Thomas Svensson、Jens Finnman、Jon H. Rasmussen

  DOI：10.1039/c9gc00898e

  日期：——

  greener synthesis of complex peptides we report that conventional one-dimensional (1D) green solid-phase peptide synthesis (SPPS) is elevated to a two-dimensional (2D) concept in which side chains in peptide resins are functionalized by suitable green tactics. Specifically, we disclose on-resin deblocking using trifluoroacetic acid (TFA)/triisopropylsilane (TIS) in EtOAc/MeCN used in a synthesis of a

  为了更绿色地合成复杂的肽，我们报告了常规的一维（1D）绿色固相肽合成（SPPS）被提升为二维（2D）概念，其中肽树脂中的侧链通过合适的绿色策略进行了功能化。具体而言，我们公开了使用三氟乙酸（TFA）/三异丙基硅烷（TIS）在EtOAc / MeCN中的树脂上解封，该合成物用于合成（i）1D绿色SPPS（ii）2D绿色SPPS的黑皮质素受体激动剂。 TFA / TIS在EtOAc / MeCN中对Lys（Mtt）和Asp（O-2-Ph i Pr）脱保护，然后使用PyBOP / DIEA在NBP / EtOAc中进行内酰胺化（iii）TFA裂解，然后使用4-甲基四氢吡喃进行绿色沉淀（ MTHP）/ n-庚烷。我们的绿色脱保护方案的另一个应用是从CTC树脂上裂解肽片段。
• β-Methylation of the Phe⁷ and Trp⁹ Melanotropin Side Chain Pharmacophores Affects Ligand−Receptor Interactions and Prolonged Biological Activity
  作者：Carrie Haskell-Luevano、Kate Toth、Lakmal Boteju、Constatin Job、Ana Maria de L. Castrucci、Mac E. Hadley、Victor J. Hruby

  DOI：10.1021/jm970018t

  日期：1997.8.1

  Topographically modified melanotropin side chain pharmacophore residues Phe(7) and Trp(9) in a cyclic peptide template (Ac-Nle(4)-c[Asp-His-Xaa(7)-Arg-Yaa(9)-Lys]-NH2) and Phe(7) in a linear peptide template (Ac-Ser-Tyr-Ser-Nle(4)-Glu-His-Xaa(7)-Arg-Trp-Gly-Lys-Pro-Val-NH2) result in differences in potency and prolonged biological activity in the frog and lizard skin bioassays. These topographic modifications included the four isomers of beta-methylphenylalanine (beta-MePhe)(7) and beta-methyltryptophan (beta-MeTrp)(9) and the two isomers of 1,2,3,4-tetrahydro-beta-carboline (Tea)(9) Modifications in the cyclic template resulted in up to a 1000-fold difference in potency for the beta-MePhe(7) stereoisomeric peptides; up to a 476-fold difference in potency resulted for the beta-MeTrp(9) peptides, and about a 50-fold difference between the Tca(9)-containing peptides. Up to a 40-fold difference in potency resulted for the beta-MePhe(7)? stereoisomeric peptides using the linear template in these assays. The relative potency racing for modifications in the cyclic template of beta-MePhe(7) were 2R,3S > 2S,3S = 2S,3R 2 > 2R,3R in the frog assay and 2S,3R > 2R,3S > 2S,3S > 2R,3R in the lizard assay. The relative potencies for modifications in the cyclic template of beta-MeTrp(9) were 2R,3S > 2R,3R > 2S,3R > 2S,3R in the frog assay and 2S,3S = 2R,3R > 2R,3S > 2S,3R in the lizard assay. The relative potencies for modifications in the cyclic template of Tca(9) were DTca > LTca in both assays, Significant differences in prolonged (residual) activities were also observed for these modified peptides and were dependent upon stereochemistry of the beta-methyl amino acid, peptide template, and bioassay system. Furthermore, comparisons of beta-MeTrp(9) stereoisomeric peptides on the frog, lizard, and human MC1 receptors suggest that structure-activity relationships on both the classical frog and lizard skin bioassays do not necessarily predict corresponding SAR profiles for the human melanocortin receptors, indicating a remarkable species specificity of the MC1 receptor requirements.