Outputs (23)

Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein (2024)
Journal Article
Allison, M., Davie, R. L., Mogg, A. J., Hampton, S. L., Emsley, J., & Stocks, M. J. (2024). Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein. ACS Medicinal Chemistry Letters, 15(4), 501–509. https://doi.org/10.1021/acsmedchemlett.3c00572

Hereditary angioedema (HAE), a rare genetic disorder, is associated with uncontrolled plasma kallikrein (PKa) enzyme activity leading to the generation of bradykinin swelling in subcutaneous and submucosal membranes in various locations of the body.... Read More about Discovery of α-Amidobenzylboronates as Highly Potent Covalent Inhibitors of Plasma Kallikrein.

Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module (2024)
Journal Article
Arce, N. A., Markham-Lee, Z., Liang, Q., Najmudin, S., Legan, E. R., Dean, G., …Li, R. (2024). Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module. Blood, https://doi.org/10.1182/blood.2023022038

Activation of von Willebrand factor (VWF) is a tightly controlled process governed primarily by local elements around its A1 domain. Recent studies suggest that the O-glycosylated sequences flanking the A1 domain constitute a discontinuous and force-... Read More about Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module.

Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections (2024)
Journal Article
Soukarieh, F., Mashabi, A., Richardson, W., Oton, E. V., Romero, M., Dubern, J., …Cámara, M. (2024). Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections. Journal of Medicinal Chemistry, 67(2), 1008-1023. https://doi.org/10.1021/acs.jmedchem.3c00973

Pseudomonas aeruginosa is one of the top priority pathogens that requires immediate attention according to the World Health Organisation (WHO). Due to the alarming shortage of novel antimicrobials, targeting quorum sensing (QS), a bacterial cell to c... Read More about Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections.

High molecular weight kininogen interactions with the homologs prekallikrein and factor XI: importance to surface-induced coagulation (2023)
Journal Article
Mohammed, B. M., Sun, M., Cheng, Q., Litvak, M., McCrae, K. R., Emsley, J., …Gailani, D. (2024). High molecular weight kininogen interactions with the homologs prekallikrein and factor XI: importance to surface-induced coagulation. Journal of Thrombosis and Haemostasis, 22(1), 225-237. https://doi.org/10.1016/j.jtha.2023.09.027

Background: In plasma, high molecular weight kininogen (HK) is either free or bound to prekallikrein (PK) or factor (F) XI (FXI). During contact activation, HK is thought to anchor PK and FXI to surfaces, facilitating their conversion to the protease... Read More about High molecular weight kininogen interactions with the homologs prekallikrein and factor XI: importance to surface-induced coagulation.

Conformational analysis and interaction of the Staphylococcus aureus transmembrane peptidase AgrB with its AgrD propeptide substrate (2023)
Journal Article
Bardelang, P., Murray, E. J., Blower, I., Zandomeneghi, S., Goode, A., Hussain, R., …Bonev, B. B. (2023). Conformational analysis and interaction of the Staphylococcus aureus transmembrane peptidase AgrB with its AgrD propeptide substrate. Frontiers in Chemistry, 11, Article 1113885. https://doi.org/10.3389/fchem.2023.1113885

Virulence gene expression in the human pathogen, S. aureus is regulated by the agr (accessory gene regulator) quorum sensing (QS) system which is conserved in diverse Gram-positive bacteria. The agr QS signal molecule is an autoinducing peptide (AIP)... Read More about Conformational analysis and interaction of the Staphylococcus aureus transmembrane peptidase AgrB with its AgrD propeptide substrate.

Structures of factor XI and prekallikrein bound to domain 6 of high–molecular weight kininogen reveal alternate domain 6 conformations and exosites (2023)
Journal Article
Li, C., Barroeta, A. B., Wong, S. S., Kim, H. J., Pathak, M., Dreveny, I., …Emsley, J. (2023). Structures of factor XI and prekallikrein bound to domain 6 of high–molecular weight kininogen reveal alternate domain 6 conformations and exosites. Journal of Thrombosis and Haemostasis, https://doi.org/10.1016/j.jtha.2023.03.042

Background: High–molecular weight kininogen (HK) circulates in plasma as a complex with zymogen prekallikrein (PK). HK is both a substrate and a cofactor for activated plasma kallikrein, and the principal exosite interactions occur between PK N-termi... Read More about Structures of factor XI and prekallikrein bound to domain 6 of high–molecular weight kininogen reveal alternate domain 6 conformations and exosites.

Characterizing the binding of glycoprotein VI with nanobody 35 reveals a novel monomeric structure of glycoprotein VI where the conformation of D1+D2 is independent of dimerization (2022)
Journal Article
Damaskinaki, F. N., Jooss, N. J., Martin, E. M., Clark, J. C., Thomas, M. R., Poulter, N. S., …Slater, A. (2023). Characterizing the binding of glycoprotein VI with nanobody 35 reveals a novel monomeric structure of glycoprotein VI where the conformation of D1+D2 is independent of dimerization. Journal of Thrombosis and Haemostasis, 21(2), 317-328. https://doi.org/10.1016/j.jtha.2022.11.002

Background: The platelet–signaling receptor glycoprotein VI (GPVI) is a promising antithrombotic target. We have previously raised a series of high-affinity nanobodies (Nbs) against GPVI and identified Nb2, Nb21, and Nb35 as potent GPVI inhibitors. T... Read More about Characterizing the binding of glycoprotein VI with nanobody 35 reveals a novel monomeric structure of glycoprotein VI where the conformation of D1+D2 is independent of dimerization.

Design and Evaluation of New Quinazolin-4(3 H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa (2021)
Journal Article
Soukarieh, F., Mashabi, A., Richardson, W., Oton, E. V., Romero, M., Roberston, S. N., …Cámara, M. (2021). Design and Evaluation of New Quinazolin-4(3 H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa. ACS Infectious Diseases, 7(9), 2666-2685. https://doi.org/10.1021/acsinfecdis.1c00175

P. aeruginosa (PA) continues to pose a threat to global public health due to its high levels of antimicrobial resistance (AMR). The ongoing AMR crisis has led to an alarming shortage of effective treatments for resistant microbes, and hence there is... Read More about Design and Evaluation of New Quinazolin-4(3 H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa.

Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR (2020)
Journal Article
Grossman, S., Soukarieh, F., Richardson, W., Liu, R., Mashabi, A., Emsley, J., …Stocks, M. J. (2020). Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR. European Journal of Medicinal Chemistry, 208, Article 112778. https://doi.org/10.1016/j.ejmech.2020.112778

© 2020 The Authors Rising numbers of cases of multidrug- and extensively drug-resistant Pseudomonas aeruginosa over recent years have created an urgent need for novel therapeutic approaches to cure potentially fatal infections. One such approach is v... Read More about Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR.

Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery (2020)
Journal Article
Kaira, B. G., Slater, A., McCrae, K. R., Dreveny, I., Sumya, U., Mutch, N. J., …Emsley, J. (2020). Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery. Blood, 136(14), 1685–1697. https://doi.org/10.1182/blood.2020004818

The contact system is composed of Factor XII (FXII), prekallikrein (PK) and co-factor kininogen (HK). The globular C1q receptor (gC1qR) has been shown to interact with FXII and HK. We reveal the FXII fibronectin type II domain (FnII) binds gC1qR in a... Read More about Factor XII and kininogen asymmetric assembly with gC1qR/C1QBP/P32 is governed by allostery.