Ac-Tyr(3-I)-D-Phe-Arg-Trp-NH2 | 1609537-60-1

• 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(3-I)-D-Phe-Arg-Trp-NH2
• 英文别名: (2S)-2-[[(2R)-2-[[(2S)-2-acetamido-3-(4-hydroxy-3-iodophenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-N-[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-5-(diaminomethylideneamino)pentanamide
• CAS: 1609537-60-1
• 化学式: C₃₇H₄₄IN₉O₆
• 分子量: 837.718
• InChiKey: DZNQKHMNZLNNRU-XHPANXIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  53
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  260
• 氢给体数：
  9
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (9-fluorenylmethoxycarbonyl)-3-iodo-O-tert-butyl-L-tyrosine 、 乙酸酐 、 Fmoc-D-苯丙氨酸 、 Fmoc-L-色氨酸(Boc)-OH 、 Fmoc-Pbf-L-精氨酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.15h， 生成 Ac-Tyr(3-I)-D-Phe-Arg-Trp-NH2
  参考文献：
  名称：

  Identification of Tetrapeptides from a Mixture Based Positional Scanning Library That Can Restore nM Full Agonist Function of the L106P, I69T, I102S, A219V, C271Y, and C271R Human Melanocortin-4 Polymorphic Receptors (hMC4Rs)

  摘要：

  Human obesity has been linked to genetic factors and single nucleotide polymorphisms (SNPs). Melanocortin-4 receptor (MC4R) SNPs have been associated with up to 6% frequency in morbidly obese children and adults. A potential therapy for individuals possessing such genetic modifications is the identification of molecules that can restore proper receptor signaling and function. These compounds could serve as personalized medications improving quality of life issues as well as alleviating diseases symptoms associated with obesity including type 2 diabetes. Several hMC4 SNP receptors have been pharmacologically characterized in vitro to have a decreased, or a lack of response, to endogenous agonists such as alpha-, beta-, and gamma(2)-melanocyte stimulating hormones (MSH) and adrenocorticotropin hormone (ACTH). Herein we report the use of a mixture based positional scanning combinatorial tetrapeptide library to discover molecules with nM full agonist potency and efficacy to the L106P, 169T, I102S, A219V, C271Y, and C271R hMC4Rs. The most potent compounds at all these hMC4R SNPs include Ac-His-(pI)DPhe-Tic-(pNO(2))DPhe-NH2, Ac-His-(pCl)DPhe-Tic-(pNO(2))DPhe-NH2, Ac-His-(pCl)DPhe-Arg-(pI)Phe-NH2, and Ac-Arg-(pCl)DPhe-Tic-(pNO(2))DPhe-NH2, revealing new ligand pharmacophore models for melanocortin receptor drug design strategies.

  DOI：

  10.1021/jm500064t