Improving Characterization of Small Molecules using Enhanced Molecular Reaction and Ionization Techniques

2021 ◽  
Author(s):  
Sandra N Majuta
Keyword(s):  
Small Molecules ◽  
Molecular Reaction

Preparation and characterization of newly developed matrix using functional γ -Fe2 O3 nanoparticles for mass spectrometry in small molecules

2016 ◽  
Vol 48 (11) ◽  
pp. 1127-1131 ◽  
Author(s):  
Shota Morimoto ◽  
Tomoya Ishikawa ◽  
Kuminori Hyodo ◽  
Takahiro Yamazaki ◽  
Shu Taira ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Small Molecules

scholarly journals Discovery and mechanism of action of small molecule inhibitors of ceramidases

2021 ◽  
Author(s):  
Sebastien Granier ◽  
Robert D Healey ◽  
Essa Saied ◽  
Xiaojing Cong ◽  
Gergely Karsai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Small Molecules ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Integral Membrane Proteins ◽  
Sphingolipid Metabolism ◽  
New Paradigm ◽  
Biophysical Characterization ◽  
Sphingosine 1 Phosphate

Sphingolipid metabolism is tightly controlled by enzymes to regulate essential processes such as energy utilisation and cell proliferation. The central metabolite is ceramide, a pro-apoptotic lipid catabolized by ceramidase enzymes to ultimately produce pro-proliferative sphingosine-1-phosphate. Human ceramidases can be soluble proteins (acid and neutral ceramidase) or integral membrane proteins (alkaline ceramidases). Increasing ceramide levels to increase apoptosis has shown efficacy as a cancer treatment using small molecules inhibiting a soluble ceramidase. Due to the transmembrane nature of alkaline ceramidases, no specific small molecule inhibitors have been reported. Here, we report novel fluorescent substrates (FRETceramides) of ceramidases that can be used to monitor enzyme activity in real-time. We use FRETceramides to discover the first drug-like inhibitors of alkaline ceramidase 3 (ACER3) which are active in cell-based assays. Biophysical characterization of enzyme:inhibitor interactions reveal a new paradigm for inhibition of lipid metabolising enzymes with non-lipidic small molecules.

scholarly journals Susceptibility of protein therapeutics to spontaneous chemical modifications by oxidation, cyclization, and elimination reactions

Amino Acids ◽  
2019 ◽  
Vol 51 (10-12) ◽  
pp. 1409-1431 ◽  
Author(s):  
Luigi Grassi ◽  
Chiara Cabrele
Keyword(s):  
Small Molecules ◽  
Three Dimensional ◽  
Drug Market ◽  
Structure And Function ◽  
Dimensional Structure ◽  
Chemical Modifications ◽  
Small Molecule Drugs ◽  
And Function ◽  
The Impact

Abstract Peptides and proteins are preponderantly emerging in the drug market, as shown by the increasing number of biopharmaceutics already approved or under development. Biomolecules like recombinant monoclonal antibodies have high therapeutic efficacy and offer a valuable alternative to small-molecule drugs. However, due to their complex three-dimensional structure and the presence of many functional groups, the occurrence of spontaneous conformational and chemical changes is much higher for peptides and proteins than for small molecules. The characterization of biotherapeutics with modern and sophisticated analytical methods has revealed the presence of contaminants that mainly arise from oxidation- and elimination-prone amino-acid side chains. This review focuses on protein chemical modifications that may take place during storage due to (1) oxidation (methionine, cysteine, histidine, tyrosine, tryptophan, and phenylalanine), (2) intra- and inter-residue cyclization (aspartic and glutamic acid, asparagine, glutamine, N-terminal dipeptidyl motifs), and (3) β-elimination (serine, threonine, cysteine, cystine) reactions. It also includes some examples of the impact of such modifications on protein structure and function.

scholarly journals Characterization of Small Molecules Inhibiting the Pro-Angiogenic Activity of the Zinc Finger Transcription Factor Vezf1

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1615 ◽  
Author(s):  
Ming He ◽  
Qianyi Yang ◽  
Allison Norvil ◽  
David Sherris ◽  
Humaira Gowher
Keyword(s):  
Transcription Factor ◽  
Small Molecules ◽  
Zinc Finger ◽  
Angiogenic Activity ◽  
Zinc Finger Transcription Factor

Abstract 130: Discovery and characterization of small molecules targeting the DNA-binding ETS domain of ERG in prostate cancer

2017 ◽  
Author(s):  
Miriam S. Butler ◽  
Mani Roshan-Moniri ◽  
Michael Hsing ◽  
Desmond Lau ◽  
Ari Kim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Binding ◽  
Small Molecules ◽  
Ets Domain
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