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RISS 인기검색어
- 검색키워드
- 저자 : Peter Vaillancourt (검색결과 2 건)
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P3 Promoter of Bovine Papillomavirus Type - 1
Choe, Joon Ho,Peter Vaillancourt,Michael Botchan 한국유전학회 1988 Genes & Genomics Vol.10 No.4
In attempt to map the structure of transcripts which contain coding sequence from the E1 and E8 ORFs of BPV-1, we have identified a new promoter which is internal to the E1 ORF. S1 nuclease protection and primer extension analysis of poly(A) cytoplasmic RNA from ID 13 cells reveal the presence of a pair of 5′ ends at nucleotides 886 and 896 which correlate well with the 5′ ends of a class of cDNA clones. In order to determine whether these 5′ ends corresponded to a functional promotor, the BPV-1 Pst I fragment from 576-1299 was tested in an in vitro transcription assay using HeLa cell extract. Primer extension analysis of the in vitro transcription products showed the presence of two cap sites which were the same as those observed for in vivo mRNA, and whose transcription was α-amanitin sensitive. Using a set of overiapping, uniformly labelled SP6 probes from nucleotides 576-1299 we showed by RNase protection analysis that the vast majority of transcripts which initiate from this promotor use the splice donor at nucleotide 1235 previously mapped. This confirms that the most abundant class of P3 cDNAs uses this leader exon. These transcripts are moderately abundant relative to the bulk of the BPV-1 mRNAs: the P3 leader exon-containing transcripts are estimated to be about 5-fold less abundant than the set of E6, E7 and E6/E7 transcripts which contain exons which use the splice donor at nucleotide 865. Analogous promotors and leader exons located in the 5′ region of the E1 ORF have been identified in HPV-6 and HPV-11.
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Multi-target-directed phenol–triazole ligands as therapeutic agents for Alzheimer's disease
Jones, Michael R.,Mathieu, Emilie,Dyrager, Christine,Faissner, Simon,Vaillancourt, Zavier,Korshavn, Kyle J.,Lim, Mi Hee,Ramamoorthy, Ayyalusamy,Wee Yong, V.,Tsutsui, Shigeki,Stys, Peter K.,Storr, Tim Royal Society of Chemistry 2017 Chemical Science Vol.8 No.8
<▼1><P>A series of multi-target-directed ligands are described that bind Cu, act as antioxidants, modulate Aβ peptide aggregation, and abolish Aβ toxicity in primary neurons.</P></▼1><▼2><P>Alzheimer's disease (AD) is a multifactorial disease that is characterized by the formation of intracellular neurofibrillary tangles and extracellular amyloid-β (Aβ) plaque deposits. Increased oxidative stress, metal ion dysregulation, and the formation of toxic Aβ peptide oligomers are all considered to contribute to the etiology of AD. In this work we have developed a series of ligands that are multi-target-directed in order to address several disease properties. 2-(1-(3-Hydroxypropyl)-1<I>H</I>-1,2,3-triazol-4-yl)phenol (<B>POH</B>), 2-(1-(2-morpholinoethyl)-1<I>H</I>-1,2,3-triazol-4-yl)phenol (<B>PMorph</B>), and 2-(1-(2-thiomorpholinoethyl)-1<I>H</I>-1,2,3-triazol-4-yl)phenol (<B>PTMorph</B>) have been synthesized and screened for their antioxidant capacity, Cu-binding affinity, interaction with the Aβ peptide and modulation of Aβ peptide aggregation, and the ability to limit Aβ<SUB>1–42</SUB>-induced neurotoxicity in human neuronal culture. The synthetic protocol and structural variance incorporated <I>via</I> click chemistry, highlights the influence of R-group modification on ligand-Aβ interactions and neuroprotective effects. Overall, this study demonstrates that the phenol–triazole ligand scaffold can target multiple factors associated with AD, thus warranting further therapeutic development.</P></▼2>
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