| 160054-42-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• CAS: 160054-42-2
• 化学式: C₁₃H₂₄N₂O₆
• 分子量: 304.343
• InChiKey: PWZFWTNSDWPITE-XKSSXDPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  21.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  124.96
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-[2'-(2-aminoethyl)-2,4'-bithiazole-4-carboxamido]propyl methyl sulfide 、 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以45%的产率得到
  参考文献：
  名称：

  Total Synthesis of Bleomycin A2 and Related Agents. 1. Synthesis and DNA Binding Properties of the Extended C-Terminus: Tripeptide S, Tetrapeptide S, Pentapeptide S, and Related Agents

  摘要：

  Full details of concise, diastereocontrolled syntheses of 2-5 and their incorporation into tri-, tetra-, and pentapeptide S, the C-terminus of bleomycin Alt are described. The extension of the studies to the synthesis of a complete set of tri- and tetrapeptide S structural analogs 29a,b and 43b-j is detailed, and their DNA binding constants (apparent K-B, calf thymus DNA) and apparent binding site sizes were determined. Consistent with past observations, the studies highlight the fact that the majority of the DNA binding affinity for bleomycin A(2) (1.0 X 10(5) M(-1)) and deglycobleomycin Aa (1.1 x 10(5) M(-1)) is embodied within N-BOC-tripeptide S (0.26 X 10(5) M(-1)). The additional comparisons of 29a (O.18 x 10(5) M(-1)), N-BOC-tetrapeptide S (0.21 x 10(5) M(-1)), 43h (0.20 x 10(5) M(-1)), and N-BOC-pentapeptide S (0.23 X 10(5) M(-1)) versus N-BOC-dipeptide S (0.10 x 10(5) M(-1)) indicate productive stabilizing binding interactions for the tripeptide S L-threonine subunit and substituent, illustrate that the entire pentanoic acid subunit of tetrapeptide S and its substituents do not significantly contribute to DNA binding affinity, and indicate that the entire beta-hydroxy-L-histidine subunit of pentapeptide S does not contribute to DNA binding affinity. With the exception of the L-threonine side chain substituent, the observations suggest that the tri- and tetrapeptide S substituent effects on the bleomycin A(2) DNA cleavage reaction are not due to substantial stabilizing binding interactions with duplex DNA. In addition, the measured apparent binding site sizes for bleomycin A(2)(3.8 base pairs), deglycobleomycin A(2) (3.9 base pairs), N-BOC-tripeptide S (3.6 base pairs), N-BOC-tetrapeptide S (3.7 base pairs), 43h (3.5 base pairs), and N-BOC-pentapeptide S (4.2 base pairs) versus N-BOC-dipeptide S (2.2 base pairs) and 29a (2.7 base pairs) suggest that it is the tripeptide S subunit of bleomycin A(2) that is fully bound to duplex DNA, that the tripeptide S L-threonine hydroxyethyl substituent detectably affects the agent interaction with duplex DNA, but that the presence or absence of the other tetrapeptide S and pentapeptide S backbone substituents do not substantially alter the binding site size or tripeptide S binding mode.

  DOI：

  10.1021/ja00092a011
• 作为产物：
  描述：

  在 lithium hydroxide 作用下， 以76%的产率得到
  参考文献：
  名称：

  Total Synthesis of Bleomycin A2 and Related Agents. 1. Synthesis and DNA Binding Properties of the Extended C-Terminus: Tripeptide S, Tetrapeptide S, Pentapeptide S, and Related Agents

  摘要：

  Full details of concise, diastereocontrolled syntheses of 2-5 and their incorporation into tri-, tetra-, and pentapeptide S, the C-terminus of bleomycin Alt are described. The extension of the studies to the synthesis of a complete set of tri- and tetrapeptide S structural analogs 29a,b and 43b-j is detailed, and their DNA binding constants (apparent K-B, calf thymus DNA) and apparent binding site sizes were determined. Consistent with past observations, the studies highlight the fact that the majority of the DNA binding affinity for bleomycin A(2) (1.0 X 10(5) M(-1)) and deglycobleomycin Aa (1.1 x 10(5) M(-1)) is embodied within N-BOC-tripeptide S (0.26 X 10(5) M(-1)). The additional comparisons of 29a (O.18 x 10(5) M(-1)), N-BOC-tetrapeptide S (0.21 x 10(5) M(-1)), 43h (0.20 x 10(5) M(-1)), and N-BOC-pentapeptide S (0.23 X 10(5) M(-1)) versus N-BOC-dipeptide S (0.10 x 10(5) M(-1)) indicate productive stabilizing binding interactions for the tripeptide S L-threonine subunit and substituent, illustrate that the entire pentanoic acid subunit of tetrapeptide S and its substituents do not significantly contribute to DNA binding affinity, and indicate that the entire beta-hydroxy-L-histidine subunit of pentapeptide S does not contribute to DNA binding affinity. With the exception of the L-threonine side chain substituent, the observations suggest that the tri- and tetrapeptide S substituent effects on the bleomycin A(2) DNA cleavage reaction are not due to substantial stabilizing binding interactions with duplex DNA. In addition, the measured apparent binding site sizes for bleomycin A(2)(3.8 base pairs), deglycobleomycin A(2) (3.9 base pairs), N-BOC-tripeptide S (3.6 base pairs), N-BOC-tetrapeptide S (3.7 base pairs), 43h (3.5 base pairs), and N-BOC-pentapeptide S (4.2 base pairs) versus N-BOC-dipeptide S (2.2 base pairs) and 29a (2.7 base pairs) suggest that it is the tripeptide S subunit of bleomycin A(2) that is fully bound to duplex DNA, that the tripeptide S L-threonine hydroxyethyl substituent detectably affects the agent interaction with duplex DNA, but that the presence or absence of the other tetrapeptide S and pentapeptide S backbone substituents do not substantially alter the binding site size or tripeptide S binding mode.

  DOI：

  10.1021/ja00092a011

文献信息

• A Systematic Evaluation of the Bleomycin A₂ <scp>l</scp>-Threonine Side Chain:  Its Role in Preorganization of a Compact Conformation Implicated in Sequence-Selective DNA Cleavage
  作者：Dale L. Boger、Timothy M. Ramsey、Hui Cai、Silvia T. Hoehn、JoAnne Stubbe

  DOI：10.1021/ja9816638

  日期：1998.9.1

  The preparation and examination of 3-7 are detailed and constitute analogues of deglycobleomycin A(2) (2) containing systematic modifications in the L-threonine side chain. The studies revealed a substantial impact of the substituent on the DNA cleavage efficiency and ratio of double strand/single strand (ds/ss) cleavage without affecting the characteristic 5'-GPy selectivity. The results of the comparisons proved consistent with conformational effects of the substituent within the linker domain which restrict the number of accessible conformations (Phi congruent to -120 degrees, Psi = 60-180 degrees) and favor adoption of a compact conformation (Phi congruent to -120 degrees, Psi congruent to 180 degrees) implicated in sequence-selective DNA cleavage. The studies also identify one potential site that may adopt two nearly equivalent turn conformations. This site may constitute one swivel point in the structure that permits access to a class of related bound structures (Psi = 60-180 degrees) adaptable to variable conformational characteristics required of multiple cleavage sites, including access to both strands of duplex DNA from a single intercalation site important for both primary and secondary DNA cleavage.