scholarly journals Bioorthogonal Reactions in Activity-Based Protein Profiling

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5994
Author(s):  
Steven H. L. Verhelst ◽  
Kimberly M. Bonger ◽  
Lianne I. Willems
Keyword(s):  
Physicochemical Properties ◽  
Late Stage ◽  
Drug Targets ◽  
Protein Profiling ◽  
Bioorthogonal Chemistry ◽  
Future Directions ◽  
Bioorthogonal Reactions ◽  
Novel Drug ◽  
Enzyme Species ◽  
Novel Drug Targets

Activity-based protein profiling (ABPP) is a powerful technique to label and detect active enzyme species within cell lysates, cells, or whole animals. In the last two decades, a wide variety of applications and experimental read-out techniques have been pursued in order to increase our understanding of physiological and pathological processes, to identify novel drug targets, to evaluate selectivity of drugs, and to image probe targets in cells. Bioorthogonal chemistry has substantially contributed to the field of ABPP, as it allows the introduction of tags, which may be bulky or have unfavorable physicochemical properties, at a late stage in the experiment. In this review, we give an overview of the bioorthogonal reactions that have been implemented in ABPP, provide examples of applications of bioorthogonal chemistry in ABPP, and share some thoughts on future directions.

scholarly journals Bio-engineering of bacterial microcompartments: a mini review

2019 ◽  
Vol 47 (3) ◽  
pp. 765-777 ◽  
Author(s):  
Sara Planamente ◽  
Stefanie Frank
Keyword(s):  
Drug Targets ◽  
Enzyme Concentration ◽  
Future Directions ◽  
Bacterial Microcompartments ◽  
Advanced Knowledge ◽  
Metabolic Activities ◽  
New Research ◽  
Novel Drug ◽  
Bio Engineering ◽  
Novel Drug Targets

AbstractBacterial microcompartments (BMCs) are protein-bound prokaryotic organelles, discovered in cyanobacteria more than 60 years ago. Functionally similar to eukaryotic cellular organelles, BMCs compartment metabolic activities in the cytoplasm, foremost to increase local enzyme concentration and prevent toxic intermediates from damaging the cytosolic content. Advanced knowledge of the functional and structural properties of multiple types of BMCs, particularly over the last 10 years, have highlighted design principles of microcompartments. This has prompted new research into their potential to function as programmable synthetic nano-bioreactors and novel bio-materials with biotechnological and medical applications. Moreover, due to the involvement of microcompartments in bacterial pathogenesis and human health, BMCs have begun to gain attention as potential novel drug targets. This mini-review gives an overview of important synthetic biology developments in the bioengineering of BMCs and a perspective on future directions in the field.

scholarly journals A Review on Novel Drug Targets and Future Directions for COVID-19 Treatment

2020 ◽  
Vol Volume 14 ◽  
pp. 77-82
Author(s):  
Yohannes Tsegyie Wondmkun ◽  
Ousman Ahmed Mohammed
Keyword(s):  
Drug Targets ◽  
Future Directions ◽  
Novel Drug ◽  
Novel Drug Targets

Novel drug targets in 2019

2020 ◽  
Vol 19 (5) ◽  
pp. 300-300 ◽  
Author(s):  
Sorin Avram ◽  
Liliana Halip ◽  
Ramona Curpan ◽  
Tudor I. Oprea
Keyword(s):  
Drug Targets ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Identification of Polo-like kinases as potential novel drug targets for influenza A virus

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Marie O. Pohl ◽  
Jessica von Recum-Knepper ◽  
Ariel Rodriguez-Frandsen ◽  
Caroline Lanz ◽  
Emilio Yángüez ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Drug Targets ◽  
Influenza A ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

10.3791/54738 ◽  
2016 ◽  
Author(s):  
Eamonn Morrison ◽  
Patty Wai ◽  
Andri Leonidou ◽  
Philip Bland ◽  
Saira Khalique ◽  
...  
Keyword(s):  
Functional Genomics ◽  
Cancer Cell ◽  
Drug Targets ◽  
Cell Spheroid ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christos Dimitrakopoulos ◽  
Sravanth Kumar Hindupur ◽  
Marco Colombi ◽  
Dritan Liko ◽  
Charlotte K. Y. Ng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Targets ◽  
Mtor Signaling ◽  
Omics Data ◽  
Genetic Changes ◽  
Genetic Aberrations ◽  
Functional Consequences ◽  
Novel Drug ◽  
Novel Drug Targets ◽  
Omics Data Integration

Abstract Background Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood. Results Here, we explored the effect of defined genetic changes on the transcriptome, proteome and phosphoproteome in twelve tumors from an mTOR-driven hepatocellular carcinoma mouse model. Using Network-based Integration of multi-omiCS data (NetICS), we detected 74 ‘mediators’ that relay via molecular interactions the effects of genetic and miRNA expression changes. The detected mediators account for the effects of oncogenic mTOR signaling on the transcriptome, proteome and phosphoproteome. We confirmed the dysregulation of the mediators YAP1, GRB2, SIRT1, HDAC4 and LIS1 in human HCC. Conclusions This study suggests that targeting pathways such as YAP1 or GRB2 signaling and pathways regulating global histone acetylation could be beneficial in treating HCC with hyperactive mTOR signaling.

Abstract P283: CCL5 Acts As A Vasoconstrictor On Penetrating Arterioles In The Cerebral Circulation By Enhancing 20-HETE Activity

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Reece F Crumpler ◽  
Huawei Zhang ◽  
Xing Fang ◽  
Shaoxun Wang ◽  
Baoying Zheng ◽  
...  
Keyword(s):  
Drug Targets ◽  
Perfusion Pressure ◽  
Synthesis Inhibitor ◽  
Atherosclerosis Risk In Communities ◽  
Cyp Enzymes ◽  
Sd Rats ◽  
Sodium Regulation ◽  
Novel Drug ◽  
The Brain ◽  
Novel Drug Targets

20-HETE is synthesized from arachidonic acid by cytochrome P450 (CYP) enzymes 4A and 4F. Inactivating mutations in the CYP enzymes that produce 20-HETE are associated with hypertension and stroke in man. We previously revealed that inactivating variants of CYP4A/F enzymes are associated with dementia in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NS) population. 20-HETE is involved with sodium regulation in the kidney and is a powerful vasoconstrictor. It was recently discovered that CCL5 and 20-HETE share the same receptor, GPR75. We previously found that 20-HETE constricts and augments the myogenic response (MR) of the middle cerebral artery (MCA) and renal afferent arteriole. However, whether CCL5 has any effect on penetrating arterioles (PAs) and interacts with 20-HETE is unknown. We found that GPR75 is expressed in PAs and pericytes in the brain. CYP4A is also expressed in pericytes and is inversely proportional to levels of GPR75 in the brain. In the present study, we found that 20-HETE contributes to the basal myogenic tone of PAs in SD rats. Administration of HET0016, a 20-HETE synthesis inhibitor, dilated the PA by 34 ± 3% (n = 6) under 10 mmHg perfusion pressure. Administration of WIT003, a 20-HETE agonist, constricted the vessel by 23 ± 4% (n = 6) under the same perfusion pressure. We found that CCL5 also reduced PA diameter by 20 ± 4% (n = 7) in SD rats under 10 mmHg perfusion pressure. Moreover, we compared the response to CCL5 in SS rats that are 20-HETE deficient and SS.CYP4A1 transgenic rats in which 20-HETE production is restored. PAs isolated from SS rats treated with 0.1 nM CCL5 constricted by 9 ± 5% (n = 6) while those treated with 10 nM constricted by 12 ± 3% (n = 6). CCL5 had a greater response in PAs from the SS.CYP4A1 strain, and the diameter of the PAs constricted by 14 ± 2% (n = 5) and 24 ± 5% (n = 5) in response to 0.1 and 10 nM CCL5, respectively. These results demonstrate that CCL5 has a direct effect on PAs similar to 20-HETE that acts via the GPR75 receptor. However, further study is needed to determine how CCL5 and 20-HETE interact to promote vasoconstriction. These studies would help further understand the involvement of 20-HETE in disease and potentially identify novel drug targets.

Sign in / Sign up

Export Citation Format

Share Document