scholarly journals A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongjun He ◽  
Stephanie A. Mowery ◽  
Joseph Chabenne ◽  
Brian Finan ◽  
John P. Mayer ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Small Molecule ◽  
Biological Study ◽  
One Pot ◽  
Site Specific ◽  
Rapid Procedure ◽  
Peptide Analogs ◽  
Chemical Conjugation ◽  
Peptide Conjugation ◽  
Biological Outcomes

Optimization of peptides for therapeutic purposes often includes chemical conjugation or modification with substituents that serve to broaden pharmacology or improve pharmacokinetics. We report a convenient and rapid procedure for one-pot, site-specific conjugation of two cysteine-containing peptides that utilizes a bivalent linker comprising maleimide and iodoacetyl functional groups. Following maleimide-mediated peptide conjugation the linker was converted from an unstable thiosuccinimide to a stable thioether bond suitable for biological study by mild aqueous hydrolysis. The procedure is exemplified by peptide-peptide, peptide-small molecule, and peptide-fatty acid conjugations. The method provides a facile approach to search for enhanced biological outcomes through additive and sustained peptide pharmacology unencumbered by the prospect of chemical rearrangement in the course of biological study.

scholarly journals Patient-Derived Three-Dimensional Cortical Neurospheres to Model Parkinson′s Disease

2021 ◽  
Author(s):  
Waseem K. Raja ◽  
Esther Neves ◽  
Christopher Burke ◽  
Xin Jiang ◽  
Ping Xu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Small Molecule ◽  
Three Dimensional ◽  
Underlying Disease ◽  
Alpha Synuclein ◽  
Protein Accumulation ◽  
Molecule Inhibitor ◽  
Induced Pluripotent ◽  
Small Molecule Therapeutics

There are currently no preventive or disease-modifying therapies for Parkinson′s Disease (PD). Failures in clinical trials necessitate a re-evaluation of existing pre-clinical models in order to adopt systems that better recapitulate underlying disease mechanisms and better predict clinical outcomes. In recent years, models utilizing patient-derived induced pluripotent stem cells (iPSCs) have emerged as attractive models to recapitulate disease-relevant neuropathology in vitro without exogenous overexpression of disease-related pathologic proteins. Here, we utilized iPSCs derived from patients with early-onset PD and dementia phenotypes that harbored either a point mutation (A53T) or multiplication at the Alpha-synuclein/SNCA gene locus. We generated a three-dimensional (3D) cortical neurosphere culture model to better mimic the tissue microenvironment of the brain. We extensively characterized the differentiation process using quantitative PCR, Western immunoblotting, and immunofluorescence staining. Differentiation and aging of the neurospheres revealed alterations in fatty acid profiles and elevated total and pathogenic phospho-Alpha-synuclein levels in both A53T and the triplication lines compared to their isogenic control lines. Furthermore, treatment of the neurospheres with a small molecule inhibitor of stearoyl CoA desaturase (SCD) attenuated the protein accumulation and aberrant fatty acid profile phenotypes. Our findings suggest that the 3D cortical neurosphere model is a useful tool to interrogate targets for PD and amenable to test small molecule therapeutics.

scholarly journals Synthesis of pentasubstituted 2-aryl pyrroles from boryl and stannyl alkynes via one-pot sequential Ti-catalyzed [2 + 2 + 1] pyrrole synthesis/cross coupling reactions

2020 ◽  
Vol 11 (37) ◽  
pp. 10236-10242
Author(s):  
Yukun Cheng ◽  
Channing K. Klein ◽  
Ian A. Tonks
Keyword(s):  
Small Molecule ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
One Pot ◽  
Cross Coupling Reactions

Multisubstituted pyrroles are commonly found in many bioactive small molecule scaffolds, yet the synthesis of highly-substituted pyrrole cores remains challenging.

A rapid procedure for screening and isolating oxygenated free fatty acid metabolites from plants and natural waters

Lipids ◽  
1984 ◽  
Vol 19 (4) ◽  
pp. 304-306 ◽  
Author(s):  
A. Van Rogers ◽  
Robert T. Van Aller ◽  
George F. Pessoney ◽  
Edward J. Watkins ◽  
Harold G. Leggett
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Natural Waters ◽  
Rapid Procedure ◽  
Acid Metabolites ◽  
Fatty Acid Metabolites

scholarly journals The effects of feeding suet-enriched chow on site-specific differences in the composition of triacylglycerol fatty acids in adipose tissue and its interactionsin vitrowith lymphoid cells

1997 ◽  
Vol 77 (4) ◽  
pp. 621-643 ◽  
Author(s):  
Christine A. Mattacks ◽  
Caroline M. Pond
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Lymph Nodes ◽  
Acid Composition ◽  
Guinea Pigs ◽  
Saturated Fatty Acids ◽  
Lymphoid Cells ◽  
Site Specific

The effects of diet on the composition and properties of adipose tissue in relation to lymph nodes were studied in adult guinea-pigs. The proportions of monoenoic triacylglycerol fatty acids were constant in all sites in adipose tissue of similarly fed guinea-pigs, but were substantially greater in samples from guinea-pigs fed on suet-enriched chow. Triacylglycerols in adipose tissue from near nodes contained significantly fewer saturated fatty acids, and significantly more 18:2n−6 and 18:3n−3 than those in samples from sites remote from nodes within the same depot. Depots that interact most strongly with lymphoid cellsin vitrohad the largest and most consistent within-depot differences. The gradients of triacylgiycerol fatty acid composition with distance from lymph nodes in two small intermuscular depots were similar in guinea-pigs fed on plain or suet-enriched chow. These findings are consistent with the hypothesis that adipose tissue around lymph nodes is specialized for local interactions with the lymphoid cells therein, and help to explain the variability of serial or duplicate measurements of adipose tissue composition. When cultured alone, lipopolysaccharide-stimulated lymph node lymphoid cells from suet-fed guinea-pigs incorporated as much labelled thymidine as the controls. Adipose tissue explants from suet-fed guinea-pigs inhibited lymphocyte proliferation much less than those of the controls, although the site-specific differences were similar. The pattern of site-specific differences in glycerol released from explants incubated alone was generally similar for both dietary groups, but except in the popliteal depot, the increases following co-culturing with lymphoid cells were smaller for samples from suet-fed guinea-pigs. These experiments show that minor changes in the fatty acid composition of the diet can substantially alter the interactions between adipose tissue and lymphoid cells.

One-pot preparation of polylactic acid-ibuprofen conjugates and their performance characterization

2017 ◽  
Vol 8 (45) ◽  
pp. 7009-7016 ◽  
Author(s):  
Shi-He Luo ◽  
Yan-Cheng Wu ◽  
Liang Cao ◽  
Qun-Fang Wang ◽  
Shui-Xia Chen ◽  
...  
Keyword(s):  
Polylactic Acid ◽  
One Pot ◽  
Performance Characterization ◽  
Chemical Conjugation ◽  
New Strategy

Merging esterification modification, carrier preparation, and chemical conjugation into a one-pot reaction as a new strategy for developing the polylactic acid-ibuprofen conjugates is described.

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