D-Ala-D-Ala-OtBu | 58177-82-5

• 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: D-Ala-D-Ala-OtBu
• 英文别名: (R)-tert-butyl 2-((R)-2-aminopropanamido)propanoate；tert-butyl (2R)-2-[(2R)-2-aminopropanamido]propanoate；tert-butyl (2R)-2-[[(2R)-2-aminopropanoyl]amino]propanoate
• CAS: 58177-82-5
• 化学式: C₁₀H₂₀N₂O₃
• 分子量: 216.28
• InChiKey: SVLVBJGAHGTROD-RNFRBKRXSA-N

物化性质

• 沸点：
  331.7±22.0 °C(Predicted)
• 密度：
  1.042±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  D-Ala-D-Ala-OtBu 在 palladium on activated charcoal 氢气 、 碳酸氢钠 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 3.0h， 生成 (R)-2-{(R)-2-[2-(5-Dimethylamino-naphthalene-1-sulfonylamino)-acetylamino]-propionylamino}-propionic acid tert-butyl ester
  参考文献：
  名称：

  通过筛选基于CTV的组合文库，选择能够感知d-Ala-d-Ala或d-Ala-d-Lac配体结合差异的合成受体

  摘要：

  筛选基于组合CTV的人工合成受体文库1 {1-13，1-13，1-13}以结合各种d-Ala-d-Ala和d-Ala-d-Lac配体（6 – 11）在磷酸盐缓冲液（0.1 N，pH = 7.0）中进行。经过筛选和Edman测序后，发现含有氨基酸序列的合成受体，该序列是结合染料标记的d-Ala-d-Ala或d-Ala-d-Lac配体的特征。例如，受体能够结合配体含有d-ALA-d丙氨酸6，7，9和11在他们的手臂中包含-几乎在所有情况下-至少包含一个基本氨基酸残基-主要是Lys。这与能够结合含有d-Ala-d-Lac的配体8和10的受体的臂确实是一个惊人的区别，配体8和10通常包含大量的极性氨基酸（Gln和Ser），尤其是在配体8中，但是几乎没有任何碱性氨基酸。使用不同的（荧光）染料标记表明该标记对受体的结合具有深远的影响，尽管不是决定性的。选择了用FITC-肽聚糖筛选CTV库的命中片段（6），以进行重新合成和验证。

  DOI：

  10.1016/j.tet.2004.08.074
• 作为产物：
  描述：

  tert-butyl D-alaninate 在 palladium on activated charcoal 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 D-Ala-D-Ala-OtBu
  参考文献：
  名称：

  N-末端甘氨酸席夫碱的立体控制11C-烷基化获得二肽

  摘要：

  使用各种季铵盐作为手性相转移催化剂可以进行有效的立体选择性放射化学 [11C] 烷基化，以获得功能化的二肽。我们在此报告了一种广泛适用的程序，用于二肽的不对称 [11C] 烷基化，通过使用不同的 [11C] 烷基卤化物得到标记的 N 端肽。通过使用 11C 标记的烷基卤化物、[11C] 甲基碘和 [11C] 苄基碘，观察到反应的立体选择性，并分别实现了 95:5 和 90:10 的不同专用催化剂的非对映体比例。因此，对映体富集化合物的直接合成应该在基于肽的放射性药物开发和正电子发射断层扫描成像中发挥重要作用。

  DOI：

  10.1002/ejoc.201701129

文献信息

• PRODRUGS OF CYTOTOXIC ACTIVE AGENTS HAVING ENZYMATICALLY CLEAVABLE GROUPS
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20190077752A1

  公开（公告）日：2019-03-14

  The invention relates to novel prodrugs or conjugates of the general formula (Ia) in which cytotoxic drugs, for example kinesin spindle protein inhibitors, are masked with legumain-cleavable groups and hence release the drug, and to the use of these prodrugs or conjugates for treatment and/or prevention of diseases, and to the use of these prodrugs or conjugates for production of medicaments for treatment and/or prevention of diseases, especially of hyperproliferative and/or angiogenic disorders, for example cancers.

  该发明涉及通式(Ia)的新型前药或结合物，其中细胞毒性药物，例如动力蛋白抑制剂，被腿蛋白酶可切割基团掩蔽，从而释放药物，并且涉及使用这些前药或结合物用于治疗和/或预防疾病，以及使用这些前药或结合物用于生产用于治疗和/或预防疾病的药物，特别是治疗和/或预防高增殖和/或血管生成异常的疾病，例如癌症。
• Effect of Linker Stereochemistry on the Activity of Indolinobenzodiazepine Containing Antibody–Drug Conjugates (ADCs)
  作者：Emily E. Reid、Katie E. Archer、Manami Shizuka、Alan Wilhelm、Nicholas C. Yoder、Chen Bai、Nathan E. Fishkin、Luke Harris、Erin K. Maloney、Paulin Salomon、Erica Hong、Rui Wu、Olga Ab、Shan Jin、Katharine C. Lai、Surina Sikka、Ravi V. J. Chari、Michael L. Miller

  DOI：10.1021/acsmedchemlett.9b00240

  日期：2019.8.8

  determine the role of amino acid stereochemistry on antitumor activity and tolerability, we incorporated l- and d-alanyl groups in the dipeptide, synthesized all four diastereomers, and prepared and tested the corresponding ADCs. Results of our preclinical evaluation showed that the l-Ala-l-Ala configuration provided the ADC with the highest therapeutic index (antitumor activity vs toxicity).

  结合有效的吲哚基二氮杂卓DNA烷基化剂作为有效载荷成分的抗体-药物偶联物（ADC）目前正在临床评估中。在一个ADC设计中，有效负载分子通过肽酶不稳定的连接到抗体升-Ala-升-Ala接头。为了确定氨基酸立体化学对抗肿瘤活性和耐受性的作用，我们在二肽中掺入了l和d-丙氨酰基，合成了所有四种非对映异构体，并制备并测试了相应的ADC。我们的临床前评估结果表明，l- Ala- 1 -Ala构型为ADC提供了最高的治疗指数（抗肿瘤活性与毒性）。
• Tight Binding of a Dimeric Derivative of Vancomycin with Dimeric <scp>l</scp>-Lys-<scp>d</scp>-Ala-<scp>d</scp>-Ala
  作者：Jianghong Rao、George M. Whitesides

  DOI：10.1021/ja971225l

  日期：1997.10.1

  The ligand/receptor pair consisting of a synthetic dimeric derivative of vancomycin (V), linked at the C terminus by p-xylylenediamine (V-CONHCH2C6H4CH2NHCO-V), and a dimeric derivative of L-Lys-D-Ala-D-Ala, [(CH2CONH)-H-epsilon(N-alpha-Ac)-L-Lys-D-Ala-D-Ala-CO2-](2), provides a new system with which to study the influence of divalency on the strength of binding. A competitive assay using affinity capillary electrophoresis (ACE) has been developed and used to estimate the dissociation constant of the divalent complex (K-d(d) approximate to 1.1 nM) and the enhancement in binding (similar to 10(3)) relative to the corresponding monomeric interaction between unmodified monomeric vancomycin and diacetyl-L-lys-D-Ala-D-Ala.
• A Mechanism-Based Inhibitor Targeting the <scp>dd</scp>-Transpeptidase Activity of Bacterial Penicillin-Binding Proteins
  作者：Mijoon Lee、Dusan Hesek、Maxim Suvorov、Wenlin Lee、Sergei Vakulenko、Shahriar Mobashery

  DOI：10.1021/ja038445l

  日期：2003.12.1

  Penicillin-binding proteins (PBPs) are responsible for the final stages of bacterial cell wall assembly. These enzymes are targets of beta-lactam antibiotics. Two of the PBP activities include DD-transpeptidase and DD-carboxypeptidase activities, which carry out the cross-linking of the cell wall and trimming of the peptidoglycan, the major constituent of the cell wall, by an amino acid, respectively. The activity of the latter enzyme moderates the degree of cross-linking of the cell wall, which is carried out by the former. Both these enzymes go through an acyl-enzyme species in the course of their catalytic events. Compound 6, a cephalosporin derivative incorporated with structural features of the peptidoglycan was conceived as an inhibitor specific for DD-transpeptidases. On acylation of the active sites of DD-transpeptidases, the molecule would organize itself in the two active site subsites such that it mimics the two sequestered strands of the bacterial peptidoglycan en route to their cross-linking. Hence, compound 6 is the first inhibitor conceived and designed specifically for inhibition of DD-transpeptidases. The compound was synthesized in 13 steps and was tested with recombinant PBP1b and PBP5 of Escherichia coli, a DD-transpeptidase and a DD-carboxypeptidase, respectively. Compound 6 was a time-dependent and irreversible inhibitor of PBP1b. On the other hand, compound 6 did not interact with PBP5, neither as an inhibitor (reversible or irreversible) nor as a substrate.