N-Boc-Lys(ClZ)-OH | 33640-54-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-Boc-Lys(ClZ)-OH
• 英文别名: Boc-Lys(ClZ)；(2S)-6-[(4-chlorophenyl)methoxycarbonylamino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid
• CAS: 33640-54-9
• 化学式: C₁₉H₂₇ClN₂O₆
• 分子量: 414.886
• InChiKey: YDJSVDYWIDEWFB-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.71
• 重原子数：
  28.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  113.96
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-Boc-Lys(ClZ)-OH 在 sodium hydroxide 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 3-[(S)-2-tert-Butoxycarbonylamino-6-(4-chloro-benzyloxycarbonylamino)-hexanoylamino]-benzoic acid
  参考文献：
  名称：

  Template Assembled Synthetic Proteins (TASPs). Are Template Size, Shape, and Directionality Important in Formation of Four-Helix Bundles?

  摘要：

  A series of rigid aromatic templates that vary in size, shape, and directionality have been investigated in template-assembled synthetic 4 alpha-helix peptide bundles for their capacity to enhance the alpha-helicity of an amphiphilic peptide (DAATALANALKKL-[NHCH2CH2SH]). In aqueous phosphate buffer (10 mM, pH 7) the peptide has some innate helicity (similar to 30%) which is concentration-independent between 1 and 250 mu M. Helicity is enhanced to 64-75% when 4 equiv of the peptide are connected to aromatic templates based on benzene, benzanilide, or a cyclic octapeptide. This effect is concentration-independent by circular dichroism spectroscopy (3-60 mu M [TASP]), the TASPs are monomeric by sedimentation equilibrium experiments, and have comparable thermodynamic stabilities. Thus these templates induce intra-rather than inter-molecular peptide association and are equally effective despite variations in size, shapes and directionality. When the linker between the template and peptides is sufficently long, as in these cases, TASP formation is less sensitive to the dimensions of the template than to the communication between hydrophobic peptide side chains, which are the main determinants of helix separation, 4 alpha-helix bundle size and stability. This greatly simplifies approaches to developing small molecule mimetics of interacting protein surfaces. However template size, shape, and directionality may still be important when the linker is short or when assembled peptide surfaces are isolated from one another and unable to communicate.

  DOI：

  10.1021/ja971951o

文献信息

• Design, synthesis, and in vitro activity of bis(succinimido)hexane peptide heterodimers with combined B1 and B2 antagonist activity
  作者：John C. Cheronis、Eric T. Whalley、Lisa G. Allen、Sharon D. Loy、Megan W. Elder、Matthew J. Duggan、Kelly L. Gross、James K. Blodgett

  DOI：10.1021/jm00029a006

  日期：1994.2

  based on the B2 antagonist D-Arg0-[Hyp3,D-Phe7,Leu8]-BK (1) and the B1 antagonist Lys0-[Leu8,des-Arg9]-BK (7) that are potent antagonists of both B1 and B2 receptors. From this series, compound 50 (alternatively, CP-0364), the 1,6-bis(succinimido)hexane heterodimer of D-Arg0-[Hyp3,Cys6,D-Phe7,Leu8]-BK (2), and D-Arg0-[Cys1,Hyp3,Leu8,des-Arg9]-BK (6), was found to be the most active both in vitro and

  我们基于B2拮抗剂D-Arg0- [Hyp3，D-Phe7，Leu8] -BK（1）和B1拮抗剂Lys0- [Leu8，des-Arg9] -BK（7）开发了一系列肽异二聚体是B1和B2受体的有效拮抗剂。从该系列化合物50（或者CP-0364），D-Arg0- [Hyp3，Cys6，D-Phe7，Leu8] -BK（2）和D-的1,6-双（琥珀酰亚胺基）己烷异二聚体发现Arg0- [Cys1，Hyp3，Leu8，des-Arg9] -BK（6）在体外和体内都是最活跃的。当针对缓激肽（BK）诱导的大鼠子宫平滑肌收缩进行测量时，化合物50的pA2为8.3，针对[des-Arg9] -BK诱导的兔主动脉平滑肌收缩的IC50约为10（-8）M。
• Potent vasopressin antagonist modified at the carboxy-terminal tripeptide tail
  作者：Fadia El-Fehail Ali、Hsin Lan Chang、William F. Huffman、Grace Heckman、Lewis B. Kinter、Edwin F. Weidley、Richard Edwards、Dulcie Schmidt、Daryl Ashton-Shue、Frans L. Stassen

  DOI：10.1021/jm00395a019

  日期：1987.12

  V2-receptor antagonists. Similar modification of a representative agonist drastically reduces its potency. We report the synthesis and pharmacological properties of a series of potent V2-receptor antagonists 3-9 where a combination of D or L dibasic dipeptide has been utilized to replace the common tripeptide fragment. Our results suggest a difference in the way agonists and antagonists bind to vasopressin

  在不断努力设计更有效的肾血管加压素（V2受体）拮抗剂时，我们将注意力集中在了羧基末端三肽尾巴（Pro-Arg-Gly-NH2）上，这是激动剂和拮抗剂共同的片段。直接连接在环六肽环上的具有二元二肽尾巴的加压素拮抗剂类似物是有效的V2受体拮抗剂，例如，Arg-Arg-NH2或Arg-Lys-NH2。代表性激动剂的类似修饰极大地降低了其效力。我们报告了一系列有效的V2受体拮抗剂3-9的合成和药理特性，其中D或L二元二肽的组合已被用来替代常见的三肽片段。我们的结果表明，激动剂和拮抗剂与血管加压素受体结合的方式有所不同，并进一步支持了激动剂和拮抗剂的结构活性关系上的差异。这些结果为新型V2受体拮抗剂的设计提供了潜在有用的见解。
• Design, Synthesis, and Evaluation of Phe-Gly Mimetics:  Heterocyclic Building Blocks for Pseudopeptides
  作者：Susanna Borg、Roeland C. Vollinga、Maryse Labarre、Kemal Payza、Lars Terenius、Kristina Luthman

  DOI：10.1021/jm990197+

  日期：1999.10.1

  ring systems have been synthesized as building blocks in the synthesis of pseudopeptides. Three derivatives (1-3) have the carboxylic acid function directly bound to the heterocyclic ring, and three derivatives (4-6) have an extra methylene group between the heterocyclic ring and the acid function to allow for an increased conformational flexibility. The mimetics were used as Phe-Gly replacements in

  含有1,3,4-恶二唑，1,2,4-恶二唑和1,2,4-三唑环系统的对映体杂环Boc保护的Phe-Gly二肽模拟物是伪肽合成中的结构单元。三个衍生物（1-3）具有直接键合到杂环上的羧酸官能团，并且三个衍生物（4-6）在杂环和酸官能团之间具有额外的亚甲基，以提高构象柔韧性。该模拟物用作生物活性肽dermorphin（Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH（2））和P物质（Arg-Pro-Lys-Pro-Gln的Phe-Gly替代品） -Gln-Phe-Phe-Gly-Leu-MetNH（2），SP）。使用Boc化学方法在MBHA树脂上使用固相方法进行假肽合成。通过测试dermorphin假肽的微阿片受体亲和力和SP假肽的NK（1）受体亲和力来进行生物学评估。结果表明，除3个模拟物外，其他所有模拟物均是dermorphin中Phe-Gly的极佳替代品，因为它们对微受体（IC（50）=
• Solid-phase synthesis of peptides using allylic anchoring groups. An investigation of their palladium-catalysed cleavage
  作者：Paul Lloyd-Williams、Gemma Jou、Fernando Albericio、Ernest Giralt

  DOI：10.1016/s0040-4039(00)79906-0

  日期：1991.8

  The use of two different allylic “handles” has been investigated in the solid-phase synthesis of protected peptides. Very high yields for the cleavage of peptides from the resin, under mild conditions which preserve side-chain protecting groups can be achieved by carrying out the cleavage reaction in 2:2:1 THF/DMSO/0.5 M HCl, using morpholine as nucleophile and Pd(Ph3P)4 as catalyst.

  在保护肽的固相合成中，已经研究了两种不同烯丙基“手柄”的使用。通过在2：2：1 THF / DMSO / 0.5 M HCl中使用吗啉作为亲核试剂和以Pd（Ph 3 P）4为催化剂。
• An Efficient Procedure for Synthesis of Phosphopeptides through the Benzyl Phosphate-Protection by the Boc Mode Solid-Phase Method
  作者：Tateaki Wakamiya、Kunio Saruta、Shoichi Kusumoto、Kiichiro Nakajima、Kumiko Yoshizawa-Kumagaye、Shinobu Imajoh-Ohmi、Shiro Kanegasaki

  DOI：10.1246/cl.1993.1401

  日期：1993.8

  The benzyl phosphate-protection for phosphoamino acid is very useful for Boc mode solid-phase synthesis of phosphopeptides. A phosphothreonine-containing peptide related to the EGF receptor protein was synthesized by use of this methodology.

  苄基磷酸盐对磷酸氨基酸的保护在Boc模式固相合成磷肽中非常有用。利用这种方法合成了与EGF受体蛋白相关的含磷酸苏氨酸的肽。