2'6'-Dmt-D-Arg-Phe-Lys-NH2 | 255861-98-4

• 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: 2'6'-Dmt-D-Arg-Phe-Lys-NH2
• 英文别名: H-2',6'-dimethyltyrosyl-D-Arg-Phe-Lys-NH2；2',6'-dimethyltyrosyl-D-Arg-Phe-Lys-NH2；2′,6′-dimethyltyrosine-D-Arg-Phe-Lys-NH2；2’,6’-dimethyl-Tyr-D-Arg-Phe-Lys-NH2；2′,6′-dmt-D-Arg-Phe-Lys-NH2；2’6’-Dmt-D-Arg-Phe-Lys-NH2；(2S)-6-amino-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]hexanamide
• CAS: 255861-98-4
• 化学式: C₃₂H₄₉N₉O₅
• 分子量: 639.798
• InChiKey: FIAKHZXVLBNZLW-NFGXINMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  46
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  267
• 氢给体数：
  9
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2'6'-Dmt-D-Arg-Phe-Lys-NH2 在 1,3,4,6-四氯-3α,6α-二苯基甘脲 、 sodium iodide 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.02h， 生成
  参考文献：
  名称：

  In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt¹-DALDA Analogues

  摘要：

  In this study the mu opioid receptor (MOR) ligands DALDA (Tyr-D-Arg-Phe-Lys-NH2) and Dmt(1)-DALDA (Dmt-D-Arg-Phe-Lys-NH2, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified peptide (3), all peptide analogues derivatized at the C-terminus (4-7) proved to possess high affinity and agonist potency at both MOR and DOR (delta opioid receptor). Results of the Caco-2 monolayer permeation, as well as in vitro blood-brain barrier model experiments, showed that, in the case of compound 4, the glycosylation only slightly diminished the lumen-to-blood and blood-to-lumen transport. Altogether, these experiments were indicative of transcellular transport but not active transport. In vivo assays demonstrated that the peptides were capable of (i) crossing the blood-brain barrier (BBB) and (ii) activating both the spinal ascending as well as the descending opioid pathways, as determined by the tail-flick and hot-plate assays, respectively. In contrast to the highly selective MOR agonist Dmt(1)-DALDA 1, compounds 4-7 are mixed MOR/DOR agonists, expected to produce reduced opioid-related side effects.

  DOI：

  10.1021/ml4004765
• 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 、 N6-[[(2-氯苯基)甲氧基]羰基]-L-赖氨酸 、 N-Boc-O-Boc-2',6'-dimethyl-L-tyrosine 生成 2'6'-Dmt-D-Arg-Phe-Lys-NH2
  参考文献：
  名称：

  Synthesis and in vitro opioid activity profiles of DALDA analogues

  摘要：

  The tetrapeptide DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) is a polar and selective mu agonist showing poor penetration of the placental and blood-brain barriers. In an effort to enhance the potency of DALDA, analogues containing 2',6'-dimethyltyrosine (Dmt), N,2',6'-trimethyltyrosine (Tmt), 2'-methyltyrosine (Mmt) or 2'-hydroxy,6'-methyltyrosine (Hmt) in place of Tyr(1), or Om or alpha,gamma -diaminobutyric acid (A(2)bu) in place of Lys(4), were synthesized. All compounds displayed high mu receptor selectivity in the rat and guinea pig brain membrane binding assays and most of them were more potent mu agonists than DALDA in the mu receptor-representative guinea pig ileum assay, with [Dmt(1)]DALDA showing the highest potency. Because of its extraordinary mu agonist potency, high mu selectivity, polar character (charge of 3+) and metabolic stability, [Dmt(1)]DALDA has potential for use in obstetrical or peripheral analgesia. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)01171-5

文献信息

• [EN] AROMATIC-CATIONIC PEPTIDES CONJUGATED TO ANTIOXIDANTS AND THEIR USE IN TREATING COMPLEX REGIONAL PAIN SYNDROME<br/>[FR] PEPTIDES AROMATIQUES-CATIONIQUES CONJUGUÉS À DES ANTIOXYDANTS ET LEUR UTILISATION DANS LE TRAITEMENT D'UN SYNDROME DOULOUREUX RÉGIONAL COMPLEXE
  申请人：SCHILLER PETER

  公开号：WO2017093897A1

  公开（公告）日：2017-06-08

  Compositions comprising an antioxidant directed or indirectly conjugated to an aromatic-cationic peptide are provide. Said antioxidants are selected from TEMPO, Tro, PBN, AHDP, DBHP, Caf and Hem and may be conjugated to the aromatic-cationic peptide directly or indirectly via a linker to the N-terminus, C-terminus or a side chain of an amino acid residue of the aromatic-cationic peptide. In some embodiments, the aromatic-cationic peptide is 2',6'-Dmt-D-Arg-Phe-Lys-NH2, Phe-D-Arg-Phe-Lys-NH2 or D-Arg-2',6'-Dmt-Lys-Phe-NH2. These conjugates have increased antioxidant activity as compared to the unconjugated aromatic-cationic peptide and have utility in treating complex regional pain syndrome.

  提供了包含直接或间接与芳香-阳离子肽结合的抗氧化剂的组合物。所述抗氧化剂从TEMPO、Tro、PBN、AHDP、DBHP、Caf和Hem中选择，并且可以通过连接剂直接或间接地与芳香-阳离子肽结合到N-末端、C-末端或芳香-阳离子肽的氨基酸残基的侧链。在某些实施例中，芳香-阳离子肽为2',6'-Dmt-D-Arg-Phe-Lys-NH2、Phe-D-Arg-Phe-Lys-NH2或D-Arg-2',6'-Dmt-Lys-Phe-NH2。与未结合的芳香-阳离子肽相比，这些共轭物具有增强的抗氧化活性，并可用于治疗复杂性区域性疼痛综合征。
• Therapeutic compositions including frataxin, lactoferrin, and mitochondrial energy generating enzymes, and uses thereof
  申请人：Stealth BioTherapeutics Corp

  公开号：US10576124B2

  公开（公告）日：2020-03-03

  Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of a therapeutic biological molecule, and/or naturally or artificially occurring derivatives, analogues, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide). The present technology provides compositions related to aromatic-cationic peptides linked to a therapeutic biological molecule and uses of the same. In some embodiments, the aromatic-cationic peptide comprises 2′,6′-dimethyl-Tyr-D-Arg-Phe-Lys-NH2, Phe-D-Arg-Phe-Lys-NH2, or D-Arg-2′,6′-Dmt-Lys-Phe-NH2.

  本文公开了用于治疗和/或预防疾病或病症的方法和组合物，包括施用治疗性生物分子和/或其天然或人工衍生物、类似物或药学上可接受的盐，单独或与一种或多种活性剂（如芳香阳离子肽）结合使用。本技术提供了与治疗性生物分子连接的芳香族阳离子肽相关的组合物及其用途。在一些实施方案中，芳香族阳离子肽包括2′,6′-二甲基-Tyr-D-Arg-Phe-Lys-NH2、Phe-D-Arg-Phe-Lys-NH2或D-Arg-2′,6′-Dmt-Lys-Phe-NH2。
• MEDICINAL USES OF MU-OPIOID RECEPTOR AGONISTS
  申请人：CORNELL RESEARCH FOUNDATION, INC.

  公开号：EP1303186B1

  公开（公告）日：2011-01-26
• EP1303186A4
  申请人：——

  公开号：EP1303186A4

  公开（公告）日：2007-02-07
• THERAPEUTIC COMPOSITIONS INCLUDING FRATAXIN, LACTOFERRIN, AND MITOCHONDRIAL ENERGY GENERATING ENZYMES, AND USES THEREOF
  申请人：Stealth Biotherapeutics Corp

  公开号：EP3148565A2

  公开（公告）日：2017-04-05