scholarly journals Investigation of the antimicrobial activity of soy peptides by developing a high throughput drug screening assay

2016 ◽  
Vol 6 ◽  
pp. 149-157 ◽  
Author(s):  
Rekha Dhayakaran ◽  
Suresh Neethirajan ◽  
Xuan Weng
2016 ◽  
Author(s):  
Rekha Dhayakaran ◽  
Suresh Neethirajan ◽  
Xuan Weng

Background: Antimicrobial resistance is a great concern in the medical community, as well as food industry. Soy peptides were tested against bacterial biofilms for their antimicrobial activity. A high throughput drug screening assay was developed using microfluidic technology, RAMAN spectroscopy, and optical microscopy for rapid screening of antimicrobials and rapid identification of pathogens. Methods: Synthesized PGTAVFK and IKAFKEATKVDKVVVLWTA soy peptides were tested against Pseudomonas aeruginosa and Listeria monocytogenes using a microdilution assay. Microfluidic technology in combination with Surface Enhanced RAMAN Spectroscopy (SERS) and optical microscopy was used for rapid screening of soy peptides, pathogen identification, and to visualize the impact of selected peptides. Results: The PGTAVFK peptide did not significantly affect P. aeruginosa, although it had an inhibitory effect on L. monocytogenes above a concentration of 625 uM. IKAFKEATKVDKVVVLWTA was effective against both P. aeruginosa and L. monocytogenes above a concentration of 37.2 uM. High throughput drug screening assays were able to reduce the screening and bacterial detection time to 4 h. SERS spectra was used to distinguish the two bacterial species.


Cancer ◽  
2013 ◽  
Vol 120 (4) ◽  
pp. 589-602 ◽  
Author(s):  
Katja Karjalainen ◽  
Renata Pasqualini ◽  
Jorge E. Cortes ◽  
Steven M. Kornblau ◽  
Benjamin Lichtiger ◽  
...  

2005 ◽  
Vol 2 (2) ◽  
pp. 231-238 ◽  
Author(s):  
Chad Dickey ◽  
Jason Eriksen ◽  
Adeela Kamal ◽  
Francis Burrows ◽  
Srinivas Kasibhatla ◽  
...  

2020 ◽  
Vol 3 (6) ◽  
pp. 1233-1241
Author(s):  
Kirill Gorshkov ◽  
Catherine Z. Chen ◽  
Miao Xu ◽  
Juan Carlos de la Torre ◽  
Luis Martinez-Sobrido ◽  
...  

2019 ◽  
Author(s):  
Philip Tatman ◽  
Anthony Fringuello ◽  
Denise Damek ◽  
Samy Youssef ◽  
Randy Jensn ◽  
...  

2019 ◽  
Author(s):  
Michael Gerckens ◽  
Hani Alsafadi ◽  
Darcy Wagner ◽  
Katharina Heinzelmann ◽  
Kenji Schorpp ◽  
...  

2020 ◽  
Author(s):  
S Bhatia ◽  
H Ahlert ◽  
N Dienstbier ◽  
J Schliehe-Diecks ◽  
M Sönnichsen ◽  
...  

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Ruochen Jia ◽  
Leon Kutzner ◽  
Anna Koren ◽  
Kathrin Runggatscher ◽  
Peter Májek ◽  
...  

AbstractMutations of calreticulin (CALR) are the second most prevalent driver mutations in essential thrombocythemia and primary myelofibrosis. To identify potential targeted therapies for CALR mutated myeloproliferative neoplasms, we searched for small molecules that selectively inhibit the growth of CALR mutated cells using high-throughput drug screening. We investigated 89 172 compounds using isogenic cell lines carrying CALR mutations and identified synthetic lethality with compounds targeting the ATR-CHK1 pathway. The selective inhibitory effect of these compounds was validated in a co-culture assay of CALR mutated and wild-type cells. Of the tested compounds, CHK1 inhibitors potently depleted CALR mutated cells, allowing wild-type cell dominance in the co-culture over time. Neither CALR deficient cells nor JAK2V617F mutated cells showed hypersensitivity to ATR-CHK1 inhibition, thus suggesting specificity for the oncogenic activation by the mutant CALR. CHK1 inhibitors induced replication stress in CALR mutated cells revealed by elevated pan-nuclear staining for γH2AX and hyperphosphorylation of RPA2. This was accompanied by S-phase cell cycle arrest due to incomplete DNA replication. Transcriptomic and phosphoproteomic analyses revealed a replication stress signature caused by oncogenic CALR, suggesting an intrinsic vulnerability to CHK1 perturbation. This study reveals the ATR-CHK1 pathway as a potential therapeutic target in CALR mutated hematopoietic cells.


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