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Medicinal-Pharmaceutical Chemistry Commons

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Articles 1 - 4 of 4

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Peptidylarginine Deiminases: Novel Drug Targets For Prevention Of Neuronal Damage Following Hypoxic Ischemic Insult (Hi) In Neonates., Sigrun Lange, Eridan Rocha-Ferreira, Laura Thei, Priyanka Mawjee, Kate Bennett, Paul R. Thompson, Venkataraman Subramanian, Anthony P. Nicholas, Donald Peebles, Mariya Hristova, Gennadij Raivich Aug 2014

Peptidylarginine Deiminases: Novel Drug Targets For Prevention Of Neuronal Damage Following Hypoxic Ischemic Insult (Hi) In Neonates., Sigrun Lange, Eridan Rocha-Ferreira, Laura Thei, Priyanka Mawjee, Kate Bennett, Paul R. Thompson, Venkataraman Subramanian, Anthony P. Nicholas, Donald Peebles, Mariya Hristova, Gennadij Raivich

Thompson Lab Publications

Neonatal hypoxic ischaemic (HI) injury frequently causes neural impairment in surviving infants. Our knowledge of the underlying molecular mechanisms is still limited. Protein deimination is a post-translational modification caused by Ca(+2) -regulated peptidylarginine deiminases (PADs), a group of five isozymes that display tissue-specific expression and different preference for target proteins. Protein deimination results in altered protein conformation and function of target proteins, and is associated with neurodegenerative diseases, gene regulation and autoimmunity. In this study, we used the neonatal HI and HI/infection [lipopolysaccharide (LPS) stimulation] murine models to investigate changes in protein deimination. Brains showed increases in deiminated ...


Modulation Of Calcium-Induced Cell Death In Human Neural Stem Cells By The Novel Peptidylarginine Deiminase-Aif Pathway., Kin Pong U, Venkataraman Subramanian, Antony P. Nicholas, Paul R. Thompson, Patrizia Ferretti Jun 2014

Modulation Of Calcium-Induced Cell Death In Human Neural Stem Cells By The Novel Peptidylarginine Deiminase-Aif Pathway., Kin Pong U, Venkataraman Subramanian, Antony P. Nicholas, Paul R. Thompson, Patrizia Ferretti

Thompson Lab Publications

PADs (peptidylarginine deiminases) are calcium-dependent enzymes that change protein-bound arginine to citrulline (citrullination/deimination) affecting protein conformation and function. PAD up-regulation following chick spinal cord injury has been linked to extensive tissue damage and loss of regenerative capability. Having found that human neural stem cells (hNSCs) expressed PAD2 and PAD3, we studied PAD function in these cells and investigated PAD3 as a potential target for neuroprotection by mimicking calcium-induced secondary injury responses. We show that PAD3, rather than PAD2 is a modulator of cell growth/death and that PAD activity is not associated with caspase-3-dependent cell death, but is required ...


Metal Stopping Reagents Facilitate Discontinuous Activity Assays Of The De Novo Purine Biosynthesis Enzyme Pure, Kelly L. Sullivan, Loredana C. Huma, Elwood Mullins, Michael E. Johnson, T. Joseph Kappock May 2014

Metal Stopping Reagents Facilitate Discontinuous Activity Assays Of The De Novo Purine Biosynthesis Enzyme Pure, Kelly L. Sullivan, Loredana C. Huma, Elwood Mullins, Michael E. Johnson, T. Joseph Kappock

Department of Biochemistry Faculty Publications

The conversion of 5-aminoimidazole ribonucleotide (AIR) to 4-carboxy-AIR (CAIR) represents an unusual divergence in purine biosynthesis: microbes and nonmetazoan eukaryotes use class I PurEs while animals use class II PurEs. Class I PurEs are therefore a potential antimicrobial target; however, no enzyme activity assay is suitable for high throughput screening (HTS). Here we report a simple chemical quench that fixes the PurE substrate/product ratio for 24 h, as assessed by the Bratton-Marshall assay (BMA) for diazotizable amines. The ZnSO4 stopping reagent is proposed to chelate CAIR, enabling delayed analysis of this acid-labile product by BMA or other HTS ...


A Nmr Experiment For Simultaneous Correlations Of Valine And Leucine/Isoleucine Methyls With Carbonyl Chemical Shifts In Proteins, Vitali Tugarinov, Vincenzo Venditti, G. Marius Clore Jan 2014

A Nmr Experiment For Simultaneous Correlations Of Valine And Leucine/Isoleucine Methyls With Carbonyl Chemical Shifts In Proteins, Vitali Tugarinov, Vincenzo Venditti, G. Marius Clore

Vincenzo Venditti

A methyl-detected ‘out-and-back’ NMR experiment for obtaining simultaneous correlations of methyl resonances of valine and isoleucine/leucine residues with backbone carbonyl chemical shifts, SIM-HMCM(CGCBCA)CO, is described. The developed pulse-scheme serves the purpose of convenience in recording a single data set for all Ileδ1, Leuδ and Valγ (ILV) methyl positions instead of acquiring two separate spectra selective for valine or leucine/isoleucine residues. The SIM-HMCM(CGCBCA)CO experiment can be used for ILV methyl assignments in moderately sized protein systems (up to ~100 kDa) where the backbone chemical shifts of 13Cα, 13Cβ and 13CO are known from prior NMR ...