SYNTHETIC STUDIES OF NEW BITHIAZOLE-AMINO ACID CONJUGATES AS DNA CLEAVERS

1.合成以2，3-二氨基丙酸、2，4-二氨基丁酸、2，5-二氨基戊酸、2，6-二氨基己酸、精氨酸、组氨酸、丙氨酸、β-丙氨酸、甘氨酸和氨基烷酸为氨基酸残基的新型联噻唑-氨基酸结合物。其中13个为2，2‘-双(氨乙基)-4，4’-联噻唑的氨乙基上的N-取代衍生物，另外6个为两个氨乙基上的N-取代的衍生物。此外，还合成了两个以2，4‘-联噻唑环作为DNA识别位点的偶联物。DNA裂解反应-所有获得的结合物的DNA裂解反应仅在Co(II)离子存在下发生。此外，DNA的裂解反应依赖于反应溶液的pH。具有一个或两个氨基酸取代基的偶联物，如2，3-二氨基丙酸，具有很强的DNA切割能力。具有一个氨基酸取代基偶联物具有更强的…比那些有两个取代基的DNA切割器更多。另一方面，以一个或两个2，3-二氨基丙酸残基为取代基的偶合物具有几乎相同的切割能力。除了2，3-二氨基丙酸外，具有一个取代基二氨基烷酸的共轭化合物比2，2‘-二(氨基乙基)-4，4’-联噻唑具有更多的氨基作为阳离子中心，因此对DNA具有很强的亲和力。此外，具有两个赖氨酸残基的结合物与DNA的亲和力最强，所得到的联噻唑-氨基酸结合物的数目和α-氨基的电离对DNA的切割能力和对DNA的亲和力起着重要作用。合成了5种新的含氨基烷基团的2，4‘-二噻唑-4-甲酰胺类化合物，并研究了它们与DNA的亲和力。结果表明，与DNA的亲和力不仅与氨基的数目有关，而且与2，4’-联噻唑环的存在有关。较少

1. SynthesisNew bithiazole-amino acid conjugates containing 2,3-diaminopropanoic acid, 2,4-diaminobutanoic acid, 2,5-diaminopentanoic acid, 2,6-diaminohexanoic acid, arginine, histidine, alanine, β-alanine, glycine, and aminoalkanoic acid as amino acid residues were readily synthesized. The thirteen synthesized conjugates are N-substituted derivatives at one of aminoethyl group of 2,2'-bis (aminoethyl)-4,4'-bithiazole and other six conjugates are N-substituted derivatives at both aminoethyl groups. Also, two conjugates possessing 2,4'-bithiazole ring as a recognition site for DNA were also synthesized.2. DNA cleavage reactionsDNA cleavage reactions of the all obtained conjugates occurred only in the presence of Co (II) ion. Also, the reactions of DNA cleavage are dependent on pH of reaction solution. The conjugates having one or two amino acid substituent such as 2,3-diaminopropanoic acid possess strong DNA cleaving ability. The conjugates having one amino acid substituent are more pow … More erful DNA cleavers than those having two substituents. On the other hand, the conjugates having one or two 2,3-diaminopropanoic acid residues as a substituent are almost same cleaving ability.3. Interaction with DNAThe conjugates having one substituent such as diaminoalkanoic acid except for 2,3-diaminopropanoic acid possess a strong affinity for DNA because they have more amino groups as a cationic center than those of 2,2'-bis (aminoethyl)-4,4'-bithiazole. Furthermore, the conjugates having two lysine residues indicated the strongest affinity for DNA among those having two substituents.A number and the ionization of α-amino groups of the obtained bithiazole-amine acid conjugates play an important role in the ability of the DNA cleavage and the affinity for DNA.4. New 2,4'-bithiazole-4-carboxamide derivativesFive new 2,4'-bithiazole4-carboxamide derivatives possessing aminoalkyl groups were synthesized and investigated their affinity for DNA.It was considered that not only a number of the ionized amino groups but also the presence of 2,4'-bithiazole ring are strongly affected the affinity for DNA. Less