β-Benzyl-D-aspartat

• 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: β-Benzyl-D-aspartat
• 英文别名: H-D-Asp(OBzl)-OH；(2R)-2-amino-4-oxo-4-phenylmethoxybutanoic acid
• 化学式: C₁₁H₁₃NO₄
• 分子量: 223.229
• InChiKey: VGALFAWDSNRXJK-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  94.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  β-Benzyl-D-aspartat 在 硫酸 、 水 、 sodium nitrite 作用下， 反应 27.0h， 以89%的产率得到3-(benzyloxy)-(R)-2-hydroxy-4-oxo-butyric acid
  参考文献：
  名称：

  In vitro chemoenzymatic and in vivo biocatalytic syntheses of new beauvericin analogues

  摘要：

  新的博维里菌素是通过来自昆虫病原真菌白僵菌的非核糖体肽合成酶BbBEAS合成的。通过使用白僵菌突变体或表达bbBeas基因的大肠杆菌菌株进行体外化学酶促和体内全细胞生物催化合成，产生了化学多样性。

  DOI：

  10.1039/c2cc31669b
• 作为产物：
  描述：

  叔丁氧羰基-D-天冬氨酸 4-苄酯 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 β-Benzyl-D-aspartat
  参考文献：
  名称：

  Antibody-Catalyzed Rearrangement of a Peptide Bond: Mechanistic and Kinetic Investigations

  摘要：

  Catalysis of the deamidation of asparagine residues may provide a powerful method for the deactivation of proteins. Catalytic antibodies (Gibbs et al. Science 1992, 258, 803) have been induced that catalyze the deamidation of a model dipeptide through an intermediate succinimide. Investigations of the mechanistic characteristics of two such antibodies, RG2-23C7 and RG2-2E4, revealed their ability to accelerate the hydrolysis of either the R- or S-enantiomers of the succinimide by factors of 10-500-fold to yield differing ratios of the aspartate and isoaspartate products. The mixed product ratios imply that two tetrahedral binding sites of unequal effectiveness were induced in response to the tetrahedral mimics (a phosphinate or secondary hydroxyl) within the hapten structure. The antibody RG2-2E4 also catalyzes the deamidation of either the D- or L-asparagine within the dipeptide through the intermediate cyclic imide, resulting in a multistep reaction sequence featuring a series of tetrahedral transition states. pH-rate profiles do not implicate functional groups within the antibodies' combining sites for either the deamidation or hydrolytic reactions. The strategy of bifunctional or higher order transition state mimics should provide a route to developing catalytic antibodies for reactions requiring multistep processing.

  DOI：

  10.1021/ja00122a001

文献信息

• [EN] METHODS FOR DELAYING, PREVENTING, AND TREATING ACQUIRED RESISTANCE TO RAS INHIBITORS<br/>[FR] MÉTHODES DE RETARDEMENT, DE PRÉVENTION ET DE TRAITEMENT DE LA RÉSISTANCE ACQUISE AUX INHIBITEURS DE RAS
  申请人：REVOLUTION MEDICINES INC

  公开号：WO2021257736A1

  公开（公告）日：2021-12-23

  The present disclosure relates to compositions and methods for the treatment of diseases or disorders (e.g., cancer) with bi-steric inhibitors of mTOR in combination with RAS inhibitors. Specifically, in some embodiments this disclosure includes compositions and methods for inducing apoptosis of tumor cells and/or for delaying, preventing, or treating acquired resistance to RAS inhibitors using bi-steric mTOR inhibitors.

  本公开涉及使用双-立体异构体mTOR抑制剂与RAS抑制剂联合治疗疾病或病状（例如，癌症）的配方和方法。具体而言，在某些实施方式中，本公开包括用于诱导肿瘤细胞凋亡和/或用于延迟、预防或治疗对RAS抑制剂获得性耐药性的双-立体异构体mTOR抑制剂的配方和方法。
• Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin
  作者：Shinichi Sato、Masashi Tetsuhashi、Keiko Sekine、Hiroyuki Miyachi、Mikihiko Naito、Yuichi Hashimoto、Hiroshi Aoyama

  DOI：10.1016/j.bmc.2008.02.024

  日期：2008.4

  A series of hybrid compounds of bestatin (1) and actinonin (3), which promote degradation of cellular inhibitor of apoptosis protein 1 (cIAP1), were designed and synthesized. Structure-activity relationship studies indicated that absolute configuration, hydrophobicity at the alpha-position of the internal amide carbonyl group, and the presence of a small substituent at the alpha-position of the ester

  设计并合成了一系列促进细胞凋亡蛋白1（cIAP1）降解的Bestatin（1）和actinonin（3）杂合化合物。构效关系研究表明，绝对构型，内部酰胺羰基的α位疏水性以及酯基的α位小取代基的存在是表达有效cIAP1降解的重要因素-促进活动。在制备的化合物中，HAB-5A（30b）表现出最强的活性（IC（50）= 0.53 microM）。
• ——
  作者：Matts Kågedahl、Peter W. Swaan、Carl T. Redemann、Mary Tang、Charles S. Craik、Francis C. Szoka, Jr.、Svein Øie

  DOI：10.1023/a:1012044526054

  日期：——

  human intestinal bile acid transporter to transport cholic acid conjugates with potential HIV-1 protease inhibitory activity. METHODS Cholic acid was conjugated at the 24 position of the sterol nucleus with various amino acids and amino acid analogs. The CaCo-2 cell line was used as a model to investigate the interaction of these bile acid conjugates with the human intestinal bile acid transporter. Interaction

  目的研究人肠胆汁酸转运蛋白转运具有潜在HIV-1蛋白酶抑制活性的胆酸结合物的能力。方法胆酸在固醇核的24位与各种氨基酸和氨基酸类似物结合。CaCo-2细胞系被用作模型来研究这些胆汁酸结合物与人肠道胆汁酸转运蛋白的相互作用。通过抑制牛磺胆酸的转运来定量载体和结合物之间的相互作用，并通过放射性标记的结合物在该细胞系中的转运来证实。结果当抑制牛磺胆酸转运时，与转运蛋白的最高相互作用发生在固醇核的24至29个区域周围存在单个负电荷时。第二个负电荷或正电荷显着降低了相互作用。牛磺胆酸抑制放射性标记的胆甾醇-L-Lys-ε-tBOC酯和胆甾醇-D-Asp-β-苄基酯的转运。在所有测试的化合物中，只有胆甾醇-D-Asp-β-苄基酯显示适度的HIV-1蛋白酶抑制活性，IC50为125 microM。结论具有适当立体化学的胆酸-氨基酸缀合物被人胆汁酸转运蛋白识别并转运，并显示出适度的HIV-1蛋白酶抑制活性
• Metalloproteinase inhibitors, pharmaceutical compositions containing
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：US06008243A1

  公开（公告）日：1999-12-28

  The present invention is directed to compound of the formula I: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y, and ##STR2## are as defined herein. These compounds are useful for inhibiting the activity of a metalloproteinase by contacting the metalloproteinase with an effective amount of the inventive compounds.

  本发明涉及化合物的公式I：##STR1##其中R.sub.1、R.sub.2、R.sub.3、R.sub.4、R.sub.5、X、Y和##STR2##如本文所定义。这些化合物可通过用创新化合物的有效量接触金属蛋白酶来抑制金属蛋白酶的活性。
• RAS INHIBITORS
  申请人：Revolution Medicines, Inc.

  公开号：US20210130326A1

  公开（公告）日：2021-05-06

  The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

  该披露涉及大环化合物，以及能够抑制Ras蛋白质的药物组合物和蛋白质复合物，以及它们在治疗癌症中的用途。