5-(4-(4-bromobutyramido)butyl)-2'-deoxyuridine | 186696-59-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-(4-(4-bromobutyramido)butyl)-2'-deoxyuridine
• 英文别名: 4-bromo-N-[4-[1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidin-5-yl]butyl]butanamide
• CAS: 186696-59-3
• 化学式: C₁₇H₂₆BrN₃O₆
• 分子量: 448.314
• InChiKey: WQGPLLCFHFUFIG-GZBFAFLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-(4-phthalimidobut-1-yl)-2'-deoxyuridine 在 氨 作用下， 生成 5-(4-(4-bromobutyramido)butyl)-2'-deoxyuridine
  参考文献：
  名称：

  Crosslinking oligonucleotides

  摘要：

  寡核苷酸（ODNs）包括一个与单链RNA、单链或双链DNA中的目标序列互补的序列，以及一个烷基化功能，在杂交后烷基化目标序列。适用于烷基化单链RNA（如信使RNA）的ODNs在沃森-克里克意义上与目标序列互补。适用于烷基化双链DNA的ODNs至少具有两个烷基化功能，并且在胡格斯汀或反向胡格斯汀意义上与目标序列互补。使用这些ODNs，目标序列的两条链都会被烷基化。第三类ODNs具有至少大约26个核苷酸单元的连续序列，与双链DNA的目标序列互补，且烷基化功能共价连接到连续序列中的一个核苷酸单元上。在存在重组酶的情况下，使用这类ODNs进行烷基化或交联。

  公开号：

  US05849482A1

文献信息

• Selective binding complementary oligonucleotides
  申请人：Epoch Pharmaceuticals, Inc.

  公开号：US05912340A1

  公开（公告）日：1999-06-15

  In a matched pair of oligonucleotides (ODNS) each member of the pair is complementary or substantially complementary in the Watson Crick sense to a target sequence of duplex nucleic acid where the two strands of the target sequence are themselves complementary to one another. The ODNs include modified bases of such nature that the modified base forms a stable hydrogen bonded base pair with the natural partner base, but does not form a stable hydrogen bonded base pair with its modified partner. This is accomplished when in a hybridized structure the modified base is capable of forming two or more hydrogen bonds with its natural complementary base, but only one hydrogen bond with its modified partner. Due to the lack of stable hydrogen bonding with each other, the matched pair of oligonucleotides have a melting temperature under physiological or substantially physiological conditions of approximately 40.degree. C. or less. However each of the matched ODN pair of the invention forms a substantially stable hybrid with the target sequence in each strand of the duplex nucleic acid. The hybrids of target duplex nucleic acids formed with the ODN pairs of the invention are useful for gene mapping and in diagnostic and therapeutic applications.

  在一对配对的寡核苷酸（ODNS）中，每个成员的配对成员在沃森-克里克意义上与双链核酸的目标序列互补或基本互补，其中目标序列的两条链本身是互补的。ODNS包括具有这种性质的修饰碱基，即修饰碱基与天然配对碱基形成稳定的氢键配对，但与其修饰配对碱基不形成稳定的氢键配对。当在杂交结构中，修饰碱基能够与其天然互补碱基形成两个或更多氢键，但只能与其修饰配对碱基形成一个氢键时，就实现了这一点。由于彼此之间缺乏稳定的氢键结合，配对的寡核苷酸在生理条件或基本生理条件下的熔化温度约为40摄氏度或更低。然而，本发明的每一对匹配的ODN对都与双链核酸的每条链中的目标序列形成基本稳定的杂交。使用本发明的ODN对形成的目标双链核酸的杂交对于基因定位以及诊断和治疗应用是有用的。
• Cross-linking oligonucleotides
  申请人：EPOCH Pharmaceuticals, Inc.

  公开号：US05824796A1

  公开（公告）日：1998-10-20

  This invention is directed to novel substituted nucleotide bases with a crosslinking arm which accomplish crosslinking between specific sites on adjoining strands of oligonucleotides or oligodeoxynucleotides. The invention is also directed to oligonucleotides comprising at least one of these crosslinking agents and to the use of the resulting novel oligonucleotides for diagnostic and therapeutic purposes. The crosslinking agents of the invention are of the following formula (I'): R.sub.1 --B--(CH.sub.2).sub.q --(Y).sub.r --(CH.sub.2).sub.m --A'(I') wherein, R.sub.1 is hydrogen, or a sugar moiety or analog thereof optionally substituted at its 3' or its 5' position with a phosphorus derivative attached to the sugar moiety by an oxygen and including groups Q.sub.1 Q.sub.2 and Q.sub.3 or with a reactive precursor thereof suitable for nucleotide bond formation; Q.sub.1 is hydroxy, phosphate or diphosphate; Q.sub.2 is .dbd.O or .dbd.S; Q.sub.3 is CH.sub.2 --R', S--R', O--R', or N--R'R"; each of R' and R" is independently hydrogen or C.sub.1-6 alkyl; B is a nucleic acid base or analog thereof that is a component of an oligonucleotide; Y is a functional linking group; each of m and q is independently 0 to 8, inclusive; r is 0 or 1; and A' is a leaving group. This invention is also directed to novel 3,4-disubstituted and 3,4,-trisubstituted pyrazolo\x9b3,4-d!-pyrimidines and to the use of these nucleic acid bases in the preparation of oligonucleotides. The invention includes nucleosides and mono- and oligonucleotides comprising at least one of these pyrazolopyrimidines, and to the use of the resulting novel oligonucleotides for diagnostic purposes.

  这项发明涉及一种新型的取代核苷酸碱基，具有交联臂，能够在寡核苷酸或寡脱氧核苷酸的相邻链上的特定位点之间实现交联。该发明还涉及包含至少一种这些交联剂的寡核苷酸，以及利用由此产生的新型寡核苷酸进行诊断和治疗的用途。该发明的交联剂具有以下式(I')：R₁--B--(CH₂)q--(Y)r--(CH₂)m--A'（I'），其中，R₁是氢，或者是糖基或其类似物，在其3'或5'位置可选择性地取代为通过氧原子连接到糖基的磷衍生物，包括基团Q₁、Q₂和Q₃，或者其适用于核苷酸键形成的反应前体；Q₁是羟基、磷酸酯或二磷酸酯；Q₂是.dbd.O或.dbd.S；Q₃是CH₂--R'、S--R'、O--R'或N--R'R"，其中R'和R"各自独立地是氢或C₁-₆烷基；B是核酸碱基或其类似物，是寡核苷酸的组成部分；Y是功能性连接基团；m和q各自独立地为0至8（包括8）；r为0或1；A'是一个脱离基团。该发明还涉及新型的3,4-二取代和3,4-三取代吡唑嘧啶，以及在制备寡核苷酸中使用这些核酸碱基。该发明包括含有至少一种这些吡唑嘧啶的核苷和单核苷酸、寡核苷酸，以及利用由此产生的新型寡核苷酸进行诊断的用途。
• Bifunctional Crosslinking oligonucleotides adapted for linking to a target sequence of duplex DNA
  申请人：Epoch Pharmaceuticals, Inc.

  公开号：US06312953B1

  公开（公告）日：2001-11-06

  Chemically modified oligonucleotides (ODNS) are complementary, either in the sense of the classic “four letter code” recognition motif, or in the sense required for triple strand formation based on the more limited “two letter code recognition motif”, to a target sequence of double stranded DNA of an invading cell, organism or pathogen, such as a virus, fungus, parasite, bacterium, malignant cell, or any duplex DNA which is desired to be broken into segments for the purpose of “mapping”. The ODNs have cross-linking agents covalently attached at least to two different sites of the ODN. Alternatively, the cross-linking agent which is attached to one site on the ODN has two cross-linking functionalities, and therefore in effect comprises two cross-linking agents. The cross-linking agent typically includes a linker arm (such as an alkyl, alkoxy, aminoalkyl or amidoalkyl chain) and a reactive group which, after triple strand formation with the target sequence of DNA, is capable of reacting with the target DNA to form a covalent bond therewith. Each cross-linking agent of the novel modified ODNs is capable of forming a covalent bond with the target DNA. As a result of the covalent bond formation between the modified ODN and both strands of the target DNA sequence, replication and expression of the target DNA sequence is inhibited. Alternatively the duplex DNA is selectively cleaved with enzymes or amino acids, at the alkylation sites for “mapping” or other investigative purposes.

  化学修饰的寡核苷酸（ODNS）与侵入细胞、生物或病原体（如病毒、真菌、寄生虫、细菌、恶性细胞或任何需要分段“映射”的双链DNA）的靶序列互补，可以是经典的“四字母代码”识别基序的意义，也可以是基于更有限的“两字母代码识别基序”的三链体形成所需的意义。ODNS上至少连接有两个不同位点的交联剂。或者，连接在ODNS上的交联剂具有两个交联功能，因此实际上包含两个交联剂。交联剂通常包括一个连接臂（例如烷基、烷氧基、氨基烷基或酰胺基烷基链）和一个反应基团，在与DNA的靶序列形成三链体后，能够与靶DNA反应形成共价键。新型修饰的ODNS的每个交联剂都能够与靶DNA形成共价键。由于修饰的ODNS与靶DNA序列的两条链之间形成共价键，因此抑制了靶DNA序列的复制和表达。或者，双链DNA可在烷基化位点上通过酶或氨基酸选择性切割，用于“映射”或其他调查目的。
• EP0472648A4
  申请人：——

  公开号：EP0472648A4

  公开（公告）日：1992-09-16
• CROSSLINKING OLIGONUCLEOTIDES
  申请人：MICROPROBE CORPORATION

  公开号：EP0472648A1

  公开（公告）日：1992-03-04