Affiliation: Leiden University
Country: The Netherlands
- Massink A, Holzheimer M, HÃ¶lscher A, Louvel J, Guo D, Spijksma G, et al. Mass spectrometry-based ligand binding assays on adenosine A1 and A2A receptors. Purinergic Signal. 2015;11:581-94 pubmed publisher..The results demonstrate the feasibility of the MS binding assay, even in the absence of a deuterium-labeled internal standard, and provide great promise for the further development of label-free assays based on MS for other GPCRs. ..
- Lenselink E, Beuming T, van Veen C, Massink A, Sherman W, Van Vlijmen H, et al. In search of novel ligands using a structure-based approach: a case study on the adenosine A2A receptor. J Comput Aided Mol Des. 2016;30:863-874 pubmed..None of these eight molecules were found to be active. Based on these results we discuss the advantages of structure-based methods and the challenges associated with finding chemically novel molecules for well-explored targets. ..
- Hillger J, Diehl C, Van Spronsen E, Boomsma D, Slagboom P, Heitman L, et al. Getting personal: Endogenous adenosine receptor signaling in lymphoblastoid cell lines. Biochem Pharmacol. 2016;115:114-22 pubmed publisher..While further validation is needed to confirm genotype-specific effects, this set-up clearly demonstrated that LCLs are a suitable model system to study genetic influences on A2AR response in particular and GPCR responses in general. ..
- Guo D, Dijksteel G, van Duijl T, Heezen M, Heitman L, Ijzerman A. Equilibrium and kinetic selectivity profiling on the human adenosine receptors. Biochem Pharmacol. 2016;105:34-41 pubmed publisher..Our proposed combinational strategy could be considered for future medicinal chemistry efforts and aid the design and discovery of different or even better leads for clinical applications. ..
- Nederpelt I, Vergroesen R, IJzerman A, Heitman L. Persistent GnRH receptor activation in pituitary Î±T3-1 cells analyzed with a label-free technology. Biosens Bioelectron. 2016;79:721-7 pubmed publisher..Moreover, this real-time monitoring allows the examination of binding kinetics and its influence on receptor activation at a cellular level. ..
- Yu Z, van Veldhoven J, t Hart I, Kopf A, Heitman L, Ijzerman A. Synthesis and biological evaluation of negative allosteric modulators of the Kv11.1(hERG) channel. Eur J Med Chem. 2015;106:50-9 pubmed publisher..1 blockers. ..
- Guo D, Heitman L, Ijzerman A. The Role of Target Binding Kinetics in Drug Discovery. ChemMedChem. 2015;10:1793-6 pubmed publisher..In this viewpoint we explore the molecular determinants of binding kinetics and discuss challenges for future binding kinetics studies. A scheme for future kinetics-directed drug design and discovery is also proposed. ..
- Liu R, Wong W, Ijzerman A. Human G protein-coupled receptor studies in Saccharomyces cerevisiae. Biochem Pharmacol. 2016;114:103-15 pubmed publisher..We describe 11 families of GPCRs in detail, while including the principles and developments of each yeast system applied to these different GPCRs and highlight and generalize the experimental findings of GPCR function in these systems. ..
- Liu R, van Veldhoven J, Ijzerman A. The role of the C-terminus of the human hydroxycarboxylic acid receptors 2 and 3 in G protein activation using GÎ±-engineered yeast cells. Eur J Pharmacol. 2016;770:70-7 pubmed publisher..This study provides new insights into the G protein coupling profiles of the HCA receptors and the function of the receptor's C terminus, which may be extended to other GPCRs. ..
- van Meer B, de Vries H, Firth K, van Weerd J, Tertoolen L, Karperien H, et al. Small molecule absorption by PDMS in the context of drug response bioassays. Biochem Biophys Res Commun. 2017;482:323-328 pubmed publisher..We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS. ..
- Hillger J, Lieuw W, Heitman L, Ijzerman A. Label-free technology and patient cells: from early drug development to precision medicine. Drug Discov Today. 2017;22:1808-1815 pubmed publisher..Applications extend as far as tissue-on-a-chip models. Thus, applying label-free technologies to patient samples can produce highly biorelevant data and, with them, unique opportunities for drug development and precision medicine. ..
- Guo D, Ijzerman A. Molecular Basis of Ligand Dissociation from G Protein-Coupled Receptors and Predicting Residence Time. Methods Mol Biol. 2018;1705:197-206 pubmed publisher..We particularly focus on the molecular basis of ligand dissociation from GPCRs and provide case studies that predict ligand dissociation pathways and residence time. ..