ORCID Profile
0000-0002-5765-4342
Current Organisation
University of Nottingham
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 31-03-2020
DOI: 10.1126/SCISIGNAL.AAZ3140
Abstract: Low intrinsic efficacy can explain the reduced side effects of apparently biased μ-opioid receptor agonists.
Publisher: American Chemical Society (ACS)
Date: 29-06-2019
DOI: 10.1021/ACS.JMEDCHEM.9B00665
Abstract: A high-throughput screen for inhibitors of the histone acetyltransferase, KAT6A, led to identification of an aryl sulfonohydrazide derivative (CTX-0124143) that inhibited KAT6A with an IC
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6OB00270F
Abstract: This paper describes the synthesis of polymers and silica nanoparticles, both bearing polystyrene sulfonate brushes, and the measurement of their binding affinity for the chemokine monocyte chemoattractant protein-1 (MCP-1) in monomeric and dimeric form.
Publisher: Elsevier BV
Date: 10-2018
Publisher: MDPI AG
Date: 15-05-2019
DOI: 10.3390/IJMS20102417
Abstract: Leukocyte migration, a hallmark of the inflammatory response, is stimulated by the interactions between chemokines, which are expressed in injured or infected tissues, and chemokine receptors, which are G protein-coupled receptors (GPCRs) expressed in the leukocyte plasma membrane. One mechanism for the regulation of chemokine receptor signaling is biased agonism, the ability of different chemokine ligands to preferentially activate different intracellular signaling pathways via the same receptor. To identify features of chemokines that give rise to biased agonism, we studied the activation of the receptor CCR1 by the chemokines CCL7, CCL8, and CCL15(Δ26). We found that, compared to CCL15(Δ26), CCL7 and CCL8 exhibited biased agonism towards cAMP inhibition and away from β-Arrestin 2 recruitment. Moreover, N-terminal substitution of the CCL15(Δ26) N-terminus with that of CCL7 resulted in a chimera with similar biased agonism to CCL7. Similarly, N-terminal truncation of CCL15(Δ26) also resulted in signaling bias between cAMP inhibition and β-Arrestin 2 recruitment signals. These results show that the interactions of the chemokine N-terminal region with the receptor transmembrane region play a key role in selecting receptor conformations coupled to specific signaling pathways.
Publisher: Elsevier BV
Date: 03-2019
Publisher: Wiley
Date: 23-05-2017
Abstract: UL22A is an 83 amino acid chemokine-binding protein produced by human cytomegalovirus that likely assists the virus in d ening the host antiviral response. We proposed that UL22A is sulfated on two tyrosine residues and tested this hypothesis through the chemical synthesis of a small library of differentially sulfated protein variants. The (sulfo)proteins were efficiently prepared using a novel β-selenoleucine motif to facilitate one-pot ligation-deselenization chemistry. Tyrosine sulfation of UL22A proved critical for RANTES binding, with the doubly sulfated variant exhibiting an improvement in binding of 2.5 orders of magnitude compared to the unmodified protein.
Publisher: Wiley
Date: 23-05-2017
Publisher: American Chemical Society (ACS)
Date: 02-03-2020
Publisher: MDPI AG
Date: 07-02-2017
DOI: 10.3390/IJMS18020342
Publisher: American Chemical Society (ACS)
Date: 19-07-2023
Publisher: American Chemical Society (ACS)
Date: 14-05-2021
Publisher: American Chemical Society (ACS)
Date: 20-05-2021
Publisher: American Association for the Advancement of Science (AAAS)
Date: 16-02-2021
DOI: 10.1126/SCISIGNAL.ABF9803
Abstract: Incorrect data entries in tables in the paper and Supplementary Materials have been corrected.
Publisher: eLife Sciences Publications, Ltd
Date: 27-01-2020
DOI: 10.7554/ELIFE.52189
Abstract: By analyzing and simulating inactive conformations of the highly homologous dopamine D2 and D3 receptors (D2R and D3R), we find that eticlopride binds D2R in a pose very similar to that in the D3R/eticlopride structure but incompatible with the D2R/risperidone structure. In addition, risperidone occupies a sub-pocket near the Na+ binding site, whereas eticlopride does not. Based on these findings and our experimental results, we propose that the ergent receptor conformations stabilized by Na+-sensitive eticlopride and Na+-insensitive risperidone correspond to different degrees of inverse agonism. Moreover, our simulations reveal that the extracellular loops are highly dynamic, with spontaneous transitions of extracellular loop 2 from the helical conformation in the D2R/risperidone structure to an extended conformation similar to that in the D3R/eticlopride structure. Our results reveal previously unappreciated ersity and dynamics in the inactive conformations of D2R. These findings are critical for rational drug discovery, as limiting a virtual screen to a single conformation will miss relevant ligands.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-05-2017
DOI: 10.1126/SCISIGNAL.AAI8529
Abstract: Chemokines and their receptors collectively orchestrate the trafficking of leukocytes in normal immune function and inflammatory diseases. Different chemokines can induce distinct responses at the same receptor. In comparison to monocyte chemoattractant protein-1 (MCP-1 also known as CCL2), the chemokines MCP-2 (CCL8) and MCP-3 (CCL7) are partial agonists of their shared receptor CCR2, a key regulator of the trafficking of monocytes and macrophages that contribute to the pathology of atherosclerosis, obesity, and type 2 diabetes. Through experiments with chimeras of MCP-1 and MCP-3, we identified the chemokine amino-terminal region as being the primary determinant of both the binding and signaling selectivity of these two chemokines at CCR2. Analysis of CCR2 mutants showed that the chemokine amino terminus interacts with the major subpocket in the transmembrane helical bundle of CCR2, which is distinct from the interactions of some other chemokines with the minor subpockets of their receptors. These results suggest the major subpocket as a target for the development of small-molecule inhibitors of CCR2.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Wiley
Date: 22-08-2023
DOI: 10.1111/BPH.16199
Abstract: Opioid‐induced respiratory depression limits the use of μ‐opioid receptor agonists in clinical settings and is the main cause of opioid overdose fatalities. The relative potential of different opioid agonists to induce respiratory depression at doses exceeding those producing analgesia is understudied despite its relevance to assessments of opioid safety. Here we evaluated the respiratory depressant and anti‐nociceptive effects of three novel opioids and relate these measurements to their in vitro efficacy. Respiration was measured in awake, freely moving male CD‐1 mice using whole body plethysmography. Anti‐nociception was measured using the hot plate test. Morphine, oliceridine and tianeptine were administered intraperitoneally, whereas methadone, oxycodone and SR‐17018 were administered orally. Receptor activation and arrestin‐3 recruitment were measured in HEK293 cells using BRET assays. Across the dose ranges examined, all opioids studied depressed respiration in a dose‐dependent manner, with similar effects at the highest doses, and with tianeptine and oliceridine showing reduced duration of effect, when compared with morphine, oxycodone, methadone and SR‐17018. When administered at doses that induced similar respiratory depression, all opioids induced similar anti‐nociception, with tianeptine and oliceridine again showing reduced duration of effect. These data were consistent with the in vitro agonist activity of the tested compounds. In addition to providing effective anti‐nociception, the novel opioids, oliceridine, tianeptine and SR‐17018 depress respiration in male mice. However, the different potencies and kinetics of effect between these novel opioids may be relevant to their therapeutic application in different clinical settings.
Publisher: Wiley
Date: 05-2018
DOI: 10.1002/PEP2.23101
Publisher: American Chemical Society (ACS)
Date: 20-01-2023
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
No related grants have been discovered for Julie Sanchez.