- Screening and in situ synthesis using crystals of a NAD kinase lead to a potent antistaphylococcal compound
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Making new ligands for a given protein by in situ ligation of building blocks (or fragments) is an attractive method. However, it suffers from inherent limitations, such as the limited number of available chemical reactions and the low information content of usual chemical library deconvolution. Here, we describe a focused screening of adenosine derivatives using X-ray crystallography. We discovered an unexpected and biocompatible chemical reactivity and have simultaneously identified the mode of binding of the resulting products. We observed that the NAD kinase from Listeria monocytogenes (LmNADK1) can promote amide formation between 5′-amino-5′- deoxyadenosine and carboxylic acid groups. This unexpected reactivity allowed us to bridge in situ two adenosine derivatives to fully occupy the active NAD site. This guided the design of a close analog showing micromolar inhibition of two human pathogenic NAD kinases and potent bactericidal activity against Staphylococcus aureus in vitro.
- Gelin, Muriel,Poncet-Montange, Guillaume,Assairi, Liliane,Morellato, Laurence,Huteau, Valerie,Dugue, Laurence,Dussurget, Olivier,Pochet, Sylvie,Labesse, Gilles
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Read Online
- 5'-Deoxidation-5'-isopropyl-substituted-amino nucleoside compound and preparing method and application thereof
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The invention discloses a 5'-deoxidation-5'-isopropyl-substituted-amino nucleoside compound shown in a formula 7, a preparing method of the compound shown in the formula 7 and application of the compound shown in the formula 7 to preparing a 5'-deoxidation-5'-polysubstitution amino nucleoside compound 1 as a midbody. The formula is defined in the description.
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Paragraph 0380-0383
(2019/05/28)
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- Diadenosine antibacterial compounds
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The present invention relates to compounds of formula (I): wherein R1, R2, R3, R4, X1, X2, X3 and Z are as defined in claim 1.The compounds are useful in the prevention and/or treatment of bacterial infections.
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Page/Page column 9-10
(2012/07/14)
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- Design, synthesis, and molecular modeling studies of 5′-deoxy-5′-ureidoadenosine: 5′-ureido group as multiple hydrogen bonding donor in the active site of S-adenosylhomocysteine hydrolase
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5′-Deoxy-5′-ureidoadenosine was designed and synthesized as a potent inhibitor of S-adenosylhomocysteine hydrolase (SAH), in which 5′-ureido group acted as multiple hydrogen bonding donor in binding with active site residues of SAH in the molecular modeli
- Wang, Ting,Lee, Hyun Joo,Tosh, Dilip K.,Kim, Hea Ok,Pal, Shantanu,Choi, Sun,Lee, Yoonji,Moon, Hyung Ryong,Zhao, Long Xuan,Lee, Kang Man,Jeong, Lak Shin
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p. 4456 - 4459
(2008/02/10)
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- Efficient reduction of azides to amines with tributylstannane. High-yield syntheses of amino and diamino deoxynucleosides
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Treatment of unprotected azido-deoxynucleosides with tributylstannane/AIBN in hot benzene/DMAC (or silyl-protected derivatives in benzene) resulted in formation of the corresponding amino-deoxynucleosides in high isolated yields. A radical process is indicated.
- Samano,Robins
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p. 6293 - 6296
(2007/10/02)
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- Synthesis and Biochemical Properties of Chemically Stable Product Analogues of the Reaction Catalyzed by S-Adenosyl-L-methionine Decarboxylase
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Structural analogues of decarboxylated S-adenosyl-L-methionine (dc-SAM), product of the reaction catalyzed by S-adenosyl-L-methionine decarboxylase (SAM-DC), with modifications in the side-chain portion of the molecule have been synthesized, and their ability to inhibit SAM-DC has been investigated.Mainly, compounds with a nitrogen atom in place of the sulfur were investigated.The data from these inhibition studies have resulted in a delineation of the structural features required for binding on SAM-DC.It was concluded that a terminal primary amino group, a terminal carboxyl group, and the sulfonium functionality are not required for binding on SAM-DC.It was also found that analogues of dc-SAM in which replacement of the sulfur by nitrogen was the only modification were still able to form an azomethine with the enzyme.As found for SAM and dc-SAM, these compounds also caused a time-dependent inactivation of SAM-DC.
- Kolb, Michael,Danzin, Charles,Barth, Jacqueline,Claverie, Nicole
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p. 550 - 556
(2007/10/02)
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