- Crystal structures and enzymatic properties of a triamine/agmatine aminopropyltransferase from thermus thermophilus
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To maintain functional conformations of DNA and RNA in high-temperature environments, an extremely thermophilic bacterium, Thermus thermophilus, employs a unique polyamine biosynthetic pathway and produces more than 16 types of polyamines. In the thermophile genome, only one spermidine synthase homolog (SpeE) was found and it was shown to be a key enzyme in the pathway. The catalytic assay of the purified enzyme revealed that it utilizes triamines (norspermidine and spermidine) and agmatine as acceptors in its aminopropyl transfer reaction; therefore, the enzyme was denoted as a triamine/agmatine aminopropyltransferase (TAAPT). We determined the crystal structures of the enzyme complexed with and without the aminopropyl group donor S-adenosylmethionine. Despite sequence and structural similarity with spermidine synthases from other organisms, a novel C-terminal β-sheet and differences in the catalytic site were observed. The C-terminal module interacts with the gatekeeping loop and fixes the open conformation of the loop to recognize larger polyamine substrates such as agmatine and spermidine. Additional computational docking studies suggest that the structural differences of the catalytic site also contribute to recognition of the aminopropyl/aminobutyl or guanidium moiety of the substrates of TAAPT. These results explain in part the extraordinarily diverse polyamine spectrum found in T. thermophilus.
- Ohnuma, Mio,Ganbe, Tadashi,Terui, Yusuke,Niitsu, Masaru,Sato, Takao,Tanaka, Nobuo,Tamakoshi, Masatada,Samejima, Keijiro,Kumasaka, Takashi,Oshima, Tairo
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- Practical synthesis of spermine, thermospermine and norspermine
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Polyamines, such as spermine (1), thermospermine (2) and norspermine (3), are widely distributed in nature, and have multiple biological activities. In addition, many of their conjugates have potential for pharmacological use. Here, we present a solid-phase synthesis using our nitrobenzenesulfonyl (Ns) strategy, which can provide 1, 2 and 3 on a gram scale. This approach should be suitable for facile construction of a diverse library of polyamines.
- Kariya, Yuka,Asanuma, Yuta,Inai, Makoto,Asakawa, Tomohiro,Ohashi-Ito, Kyoko,Fukuda, Hiroo,Egi, Masahiro,Kan, Toshiyuki
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p. 1403 - 1407
(2016/09/09)
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- METHOD FOR PRODUCING BIS-[(3-DIMETHYLAMINO)PROPYL]AMINE (DIPROPYLENE TRIAMINE, DPTA)
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The invention relates to a method for producing bis-[(3-dimethylamino)propyl]amine (dipropylene triamine, DPTA) by continuously reacting 1,3-propylene diamine (1,3-PDA) in the presence of a heterogeneous catalyst. The inventive method is characterized by
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Page/Page column 2; 3; 9
(2008/06/13)
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- Chemoenzymatic syntheses of polyamines and tetraazamacrocycles
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Syntheses of different open chain polyamines starting from enzymatically prepared bis(amidoesters) are described. Some of these polyamines are also used as precursors in the syntheses of tetraazamacrocycles. This methodology can also be applied to the synthesis of chiral compounds.
- Rubio, Mercedes,Astorga, Covadonga,Alfonso, Ignacio,Rebolledo, Francisca,Gotor, Vicente
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p. 2441 - 2452
(2007/10/03)
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- Synthesis and characterisation of polyamine-poly(ethylene glycol) constructs for DNA binding and gene delivery
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Improved non-viral vector systems are needed for efficient delivery of DNA to target cell nuclei in gene therapy. A series of linear polyamine-poly(ethylene glycol) (PEG) constructs has been synthesised by reaction of appropriately Boc-protected thermine derivatives with ω-methoxyPEG oxiranylmethyl ethers. Constructs carrying 1-3 MeOPEG units and 0, 2 or 4 N-methyl groups have been prepared by this method. H2N(CH2)3NBoc(CH2)3NBoc(CH2)3NHBoc was prepared efficiently by mono-trifluoroacetylation of thermine, attachment of Boc and removal of the trifluoroacetyl group in one pot. A similar process gave H2N(CH2)3NBoc(CH2)3NBoc(CH2)3NH2. BocMeN(CH2)3NHMe was alkylated by 1,3-dibromopropane to give BocMeN(CH2)3NMe(CH2)3NMe(CH2)3NMeBoc. A cyanoethylation/reduction sequence extended H2N(CH2)3NBoc(CH2)3NBoc(CH2)3NH2 to give H2N(CH2)3NBoc(CH2)3NBoc(CH2)3NBoc(CH2)3NBoc(CH2)3NH2, which was converted to its mono- and di-MeOPEG550 derivatives. Deprotection gave the linear polyamine-MeOPEG constructs. A branched triamine-poly(ethylene glycol) construct was prepared by acylation of (BocHN(CH2)3)2N(CH2)3NH2 with ω-methoxyPEG 550 chloroformate, followed by deprotection. A cyanoethylation/reduction/protection sequence from (H2N(CH2)3)2N(CH2)3NHBoc gave a protected pentamine. Alkylation with Br(CH2)5CONH(CH2)2NHBoc, deprotection, acylation with MeOPEG chloroformate and deprotection gave a pentamine-MeOPEG construct in which the MeOPEG is attached through a linker to the central amine. The linear hexamine construct carrying MeOPEG550 at only one terminus was the most effective DNA-interactive member of the two series in an ethidium displacement assay and was effective in delivering a reporter gene to RIF-1 tumours. Copyright (C) 2000 Elsevier Science Ltd.
- Garrett, Shane W.,Davies, Owen R.,Milroy, David A.,Wood, Pauline J.,Pouton, Colin W.,Threadgill, Michael D.
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p. 1779 - 1797
(2007/10/03)
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- KINETICS AND MECHANISM OF REACTION OF 1,3-DICHLOROPROPANE WITH AMMONIA
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The kinetics and reaction mechanism of 1,3-dichloropropane with aqueous ammonia were studied.It was shown that in the amination of 1,3-dichloropropane azetidine is hardly formed; however, intermediate reaction mixtures contain its dimer in an amount up to 10percent.A kinetic model was developed for the amination of 1,3-dichloropropane and the factors affecting the yield of reaction products were explained.
- Chernitskii, K. V.,Bobylev, V. A.
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p. 1720 - 1724
(2007/10/02)
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- CATALYTIC ALKYL GROUP EXCHANGE REACTION OF PRIMARY AND SECONDARY AMINES.
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It has been shown that primary and secondary amines undergo alkyl group exchange reactions upon treatment with palladium catalyst as depicted in an operationally simple and efficient reaction which provides a convenient method for synthesis of unsymmetrical amines. The application of the reaction for the preparation of various substituted amines and heterocyclic compounds such as hexahydropyrimidine tetrahydropyrimidine, imidazolidine, and imidazoles is described. The preparation of polyamines such as H//2N(CH//2)//mNH(CH//2)//nNH//2 (10) and H//2N(CH//2)//lNH(CH//2)//mNH(CH//2)//nNH//2 (l-n, equals 2,3; 11) is readily performed by the appadium-catalyzed reactions of azetidine (6) and aziridine (7) via azetine (9) and azirine intermediates. The mechanism the palladium-catalyzed reaction has been extensively studied on the carbonylation, racemization, and deuteurium-exchange reaction of (S)-( minus )- alpha -phenylethylamine (17).
- Murahashi,Yoshimura,Tsumiyama,Kojima
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p. 5002 - 5011
(2007/10/02)
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