| 11. |
- Emtenäs, Hans, et al.
(author)
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Design and Parallel Solid Phase Synthesis of Ring Fused 2-Pyridinones that Target Pilus Biogenesis in Pathogenic Bacteria
- 2002
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In: Journal of Combinatorial Chemistry. - : American Chemical Society (ACS). - 1520-4766 .- 1520-4774. ; 4, s. 630-639
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Journal article (peer-reviewed)abstract
- A new method for the solid-phase synthesis of enantiomerically enriched highly substituted ring-fused 2-pyridinones 13 has been developed. The synthesis mediates introduction of substituents at two positions in the 2-pyridinone ring in a diverse manner and is suitable for parallel synthesis. 19F NMR spectroscopy was used as a tool to monitor each of the five steps in the reaction sequence. The optimized conditions thus obtained were then used to prepare a library of 20 2-pyridinones with high yields. The library members were chosen from a statistical multivariate design to ensure diversity and reliable data for structure−activity relationships. Screening of the library against the bacterial periplasmic chaperone PapD was performed using surface plasmon resonance. Three new 2-pyridinones with a higher affinity for the chaperone PapD than the previous best 13{10,1} were found, and important structural features could be deduced.
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| 12. |
- Emtenäs, Hans, et al.
(author)
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Stereoselective synthesis of optically active bicyclic -lactam carboxylic acids that target pilus biogenesis in pathogenic bacteria
- 2003
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In: Organic & Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 1, s. 1308-14
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Journal article (peer-reviewed)abstract
- Optically active bicyclic -lactams were synthesized, starting from 2-H-2-thiazolines and Meldrum's acid derivatives. Several methods to accomplish an ester hydrolysis without damaging the -lactam framework were investigated. A rapid CsOH saponification of the -lactam methyl esters was developed and protonation of the Cs-carboxylates by Amberlite (IR-120 H+) afforded a series of bicyclic -lactam carboxylic acids. Moreover, a convenient method for the synthesis of 2-H-2-thiazolinecarboxylic acid methyl ester 2 was developed. Bicyclic -lactam carboxylic acids 7a–g and aldehydes 4a–d were screened for their affinity to the bacterial periplasmic chaperone PapD using a surface plasmon resonance technique. -Lactams substituted with large acyl substituents showed better binding to the chaperone than the native C-terminal peptide PapG 8, demonstrating that bicyclic -lactams constitute a new class of potential bacterial chaperone inhibitors.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Otto, C J, et al.
(author)
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The "flap" endonuclease gene FEN1 is excluded as a candidate gene implicated in the CAG repeat expansion underlying Huntington disease.
- 2001
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In: Clinical Genetics. - 0009-9163 .- 1399-0004. ; 59:2, s. 122-7
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Journal article (peer-reviewed)abstract
- At least 12 disorders including Huntington disease (HD) are associated with expansion of a trinucleotide repeat (TNR). Factors contributing to the risk of expansion of TNRs and the mechanism of expansion have not been elucidated. Data from Saccharomyces cerevisiae suggest that the flap endonuclease FEN1 plays a role in expansion of repetitive DNA tracts. It has been hypothesized that insufficiency of FEN1 or a mutant FEN1 might contribute to the occurrence of expansion events of long repetitive DNA tracts after polymerase slippage events during lagging strand synthesis. The expression pattern of FEN1 was determined, and ubiquitous tissue expression, including germ cells, suggested that FEN1 has the potential to be involved in HD. Fifteen HD parent/child pairs that demonstrated intergenerational increases in CAG length of greater than 10 repeats were examined for possible mutations or polymorphisms within the FEN1 gene that could underlie the saltatory repeat expansions seen in these individuals. No alterations were observed compared to 50 controls, excluding FEN1 as a trans-acting factor underlying TNR expansion. The identification of a candidate gene(s) in HD or other CAG-expansion disorders implicated in TNR instability will elucidate the mechanism of expansion for this growing family of neurological disorders.
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| 17. |
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| 18. |
- Rasten-Almqvist, P, et al.
(author)
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Myocarditis and sudden infant death syndrome
- 2002
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In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 0903-4641. ; 110:6, s. 469-480
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Journal article (peer-reviewed)
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| 19. |
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| 20. |
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