Dataset Information

De novo synthesis and biological evaluation of C6?-substituted C4?-amide analogues of SL0101.

ABSTRACT: In an effort to improve upon the in vivo half-life of the known ribosomal s6 kinase (RSK) inhibitor SL0101, C4?-amide/C6?-alkyl substituted analogues of SL0101 were synthesized and evaluated in cell-based assays. The analogues were prepared using a de novo asymmetric synthetic approach, which featured Pd-?-allylic catalyzed glycosylation for the introduction of a C4?-azido group. Surprisingly replacement of the C4?-acetate with a C4?-amide resulted in analogues that were no longer specific for RSK in cell-based assays.

SUBMITTER: Mrozowski RM

PROVIDER: S-EPMC4251525 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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De novo synthesis and biological evaluation of C6″-substituted C4″-amide analogues of SL0101.

Mrozowski Roman M RM Sandusky Zachary M ZM Vemula Rajender R Wu Bulan B Zhang Qi Q Lannigan Deborah A DA O'Doherty George A GA

Organic letters 20141105 22

In an effort to improve upon the in vivo half-life of the known ribosomal s6 kinase (RSK) inhibitor SL0101, C4″-amide/C6″-alkyl substituted analogues of SL0101 were synthesized and evaluated in cell-based assays. The analogues were prepared using a de novo asymmetric synthetic approach, which featured Pd-π-allylic catalyzed glycosylation for the introduction of a C4″-azido group. Surprisingly replacement of the C4″-acetate with a C4″-amide resulted in analogues that were no longer specific for R ...[more]

PMID: 25372628

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Project description:C4 photosynthesis is a carbon-concentrating mechanism that evolved independently more than 60 times in a wide range of angiosperm lineages. Among other alterations, the evolution of C4 from ancestral C3 photosynthesis requires changes in the expression of a vast number of genes. Differential gene expression analyses between closely related C3 and C4 species have significantly increased our understanding of C4 functioning and evolution. In Chenopodiaceae, a family that is rich in C4 origins and photosynthetic types, the anatomy, physiology and phylogeny of C4, C2, and C3 species of Salsoleae has been studied in great detail, which facilitated the choice of six samples of five representative species with different photosynthetic types for transcriptome comparisons. mRNA from assimilating organs of each species was sequenced in triplicates, and sequence reads were de novo assembled. These novel genetic resources were then analyzed to provide a better understanding of differential gene expression between C3, C2 and C4 species. All three analyzed C4 species belong to the NADP-ME type as most genes encoding core enzymes of this C4 cycle are highly expressed. The abundance of photorespiratory transcripts is decreased compared to the C3 and C2 species. Like in other C4 lineages of Caryophyllales, our results suggest that PEPC1 is the C4-specific isoform in Salsoleae. Two recently identified transporters from the PHT4 protein family may not only be related to the C4 syndrome, but also active in C2 photosynthesis in Salsoleae. In the two populations of the C2 species S. divaricata transcript abundance of several C4 genes are slightly increased, however, a C4 cycle is not detectable in the carbon isotope values. Most of the core enzymes of photorespiration are highly increased in the C2 species compared to both C3 and C4 species, confirming a successful establishment of the C2 photosynthetic pathway. Furthermore, a function of PEP-CK in C2 photosynthesis appears likely, since PEP-CK gene expression is not only increased in S. divaricata but also in C2 species of other groups.

Dataset Information

De novo synthesis and biological evaluation of C6?-substituted C4?-amide analogues of SL0101.

Publications

De novo synthesis and biological evaluation of C6″-substituted C4″-amide analogues of SL0101.

Similar Datasets

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