c[H-Cys-Lys-Phe-Phe-D-Trp-[4-(N-isopropyl)-aminomethyl-L-phenylalanine]-Thr-[3-(3-iodo-4-hydroxyphenyl)alanine]-Thr-Ser-Cys-OH]

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: c[H-Cys-Lys-Phe-Phe-D-Trp-[4-(N-isopropyl)-aminomethyl-L-phenylalanine]-Thr-[3-(3-iodo-4-hydroxyphenyl)alanine]-Thr-Ser-Cys-OH]
• 英文别名: H-Cys(1)-Lys-Phe-Phe-D-Trp-Phe(4-MeNHiPr)-Thr-Tyr(3-I)-Thr-Ser-Cys(1)-OH；(4R,7S,10S,13S,16S,19S,22R,25S,28S,31S,34R)-34-amino-31-(4-aminobutyl)-25,28-dibenzyl-10,16-bis[(1R)-1-hydroxyethyl]-13-[(4-hydroxy-3-iodophenyl)methyl]-7-(hydroxymethyl)-22-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27,30,33-decaoxo-19-[[4-[(propan-2-ylamino)methyl]phenyl]methyl]-1,2-dithia-5,8,11,14,17,20,23,26,29,32-decazacyclopentatriacontane-4-carboxylic acid
• 化学式: C₇₄H₉₅IN₁₄O₁₆S₂
• 分子量: 1627.69
• InChiKey: NSEQNLMYAPFUCS-JIZHMVDYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  107
• 可旋转键数：
  21
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  540
• 氢给体数：
  19
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  在 碘 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 生成 c[H-Cys-Lys-Phe-Phe-D-Trp-[4-(N-isopropyl)-aminomethyl-L-phenylalanine]-Thr-[3-(3-iodo-4-hydroxyphenyl)alanine]-Thr-Ser-Cys-OH]
  参考文献：
  名称：

  Novel, Potent, and Radio-Iodinatable Somatostatin Receptor 1 (sst₁) Selective Analogues

  摘要：

  The proposed sst(1) pharmacophore (J. Med. Chem. 2005, 48, 523-533) derived from the NMR structures of a family of mono- and dicyclic undecamers was used to design octa-, hepta-, and hexamers with high affinity and selectivity for the somatostatin sst(1) receptor. These compounds were tested for their in vitro binding properties to all five somatostatin (SRIF) receptors using receptor autoradiography; those with high SRIF receptor subtype 1 (sst(1)) affinity and selectivity were shown to be agonists when tested functionally in a luciferase reporter gene assay. Des-AA(1,4-6,10,12,13)-[DTyr(2),DAgl(NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH2 (25) was radio- iodinated (I-125-25) and specifically labeled sst(1)-expressing cells and tissues. 3D NMR structures were calculated for des-AA(1,4-6,10,12,13)- [DPhe(2),DTrp(8),IAmp(9)]-SRIF-Thr-NH2 (16), des-AA(1,2,4-6,10,12,13)-[DAgl- (NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH2 (23), and des-AA(1,2,4-6,10,12,13)-[DAgl(NMe,2naphthoyl)(8),IAmp(9),Tyr(11)]-SRIF-NH2 (27) in DMSO. Though the analogues have the sst(1) pharmacophore residues at the previously determined distances from each other, the positioning of the aromatic residues in 16, 23, and 27 is different from that described earlier, suggesting an induced fit mechanism for sst(1) binding of these novel, less constrained sst(1)- selective family members.

  DOI：

  10.1021/jm801314f

文献信息

• Novel, Potent, and Radio-Iodinatable Somatostatin Receptor 1 (sst₁) Selective Analogues
  作者：Judit Erchegyi、Renzo Cescato、Christy Rani R. Grace、Beatrice Waser、Véronique Piccand、Daniel Hoyer、Roland Riek、Jean E. Rivier、Jean Claude Reubi

  DOI：10.1021/jm801314f

  日期：2009.5.14

  The proposed sst(1) pharmacophore (J. Med. Chem. 2005, 48, 523-533) derived from the NMR structures of a family of mono- and dicyclic undecamers was used to design octa-, hepta-, and hexamers with high affinity and selectivity for the somatostatin sst(1) receptor. These compounds were tested for their in vitro binding properties to all five somatostatin (SRIF) receptors using receptor autoradiography; those with high SRIF receptor subtype 1 (sst(1)) affinity and selectivity were shown to be agonists when tested functionally in a luciferase reporter gene assay. Des-AA(1,4-6,10,12,13)-[DTyr(2),DAgl(NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH2 (25) was radio- iodinated (I-125-25) and specifically labeled sst(1)-expressing cells and tissues. 3D NMR structures were calculated for des-AA(1,4-6,10,12,13)- [DPhe(2),DTrp(8),IAmp(9)]-SRIF-Thr-NH2 (16), des-AA(1,2,4-6,10,12,13)-[DAgl- (NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH2 (23), and des-AA(1,2,4-6,10,12,13)-[DAgl(NMe,2naphthoyl)(8),IAmp(9),Tyr(11)]-SRIF-NH2 (27) in DMSO. Though the analogues have the sst(1) pharmacophore residues at the previously determined distances from each other, the positioning of the aromatic residues in 16, 23, and 27 is different from that described earlier, suggesting an induced fit mechanism for sst(1) binding of these novel, less constrained sst(1)- selective family members.