caa a22 4500 469079711 CHVBK 20180323132946.0 cr unu---uuuuu 170328e19920501xx s 000 0 eng 10.1007/BF00168949 doi (NATIONALLICENCE)springer-10.1007/BF00168949 [3H]R75231 — a new radioligand for the nitrobenzylthioinosine sensitive nucleoside transport proteins Characterization of (±)-[3H]R75231 binding to calf lung membranes, stereospecificity of its two stereoisomers, and comparison with [3H]nitrobenzylthioinosine binding [Elektronische Daten] [Adriaan IJzerman, Marieke Kruidering, Anton van Weert, Herman van Belle, Cor Janssen] Summary: The tritiated analogue of R75231 ((±)-2-(aminocarbonyl)-N-(4-amino-2,6-dichlorophenyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-1-piperazineacetamide) has been examined as a new radioligand for (nitrobenzylthioinosine sensitive) nucleoside transport proteins. [3H]R75231 was prepared in two steps from R69064 (((±)-4-[5,5-bis[4-fluorophenyl)-4-pentenyl]-2-piperazinecarboxamide dihydrochloride) with a specific activity of 0.23 TBq/mmol (6.3 Ci/mmol). [3H]R75231 bound in a pseudo-irreversible and saturable manner to a membrane preparation of calf lung tissue. The new radioligand displayed high affinity (KD = 0.32 ± 0.06 nmol/l at 25°C) and capacity (Bmax = 6.1 ± 0.3 pmol/mg protein). Specific [3H]R75231 binding could be fully displaced by both structural analogues and reference inhibitors such as dipyridamole, NBI, dilazep and hexobendine, as well as by various nucleosides. The two stereoisomers of R75231, R88016 ((+)-R75231) and R88021 ((−)-R75231), potently displaced specific [3H]R75231 and [3H]NBI binding, R88021 being 30-fold more active than R88016. Pseudo-Hill coefficients derived from the shape of all the [3H]R75231 displacement curves were approximately unity. In contrast, R75231 and most of its analogues displaced specific [3H]NBI binding with pseudo-Hill coefficients consistently larger than unity under identical experimental conditions. This latter finding is suggestive for the existence of two distinct binding sites for the two radioligands, which may or may not overlap to some extent. Springer-Verlag, 1992 [3H]R75231 nationallicence R88016 nationallicence R88021 nationallicence Nitrobenzylthioinosine nationallicence Radioligand binding nationallicence Nucleoside transport (protein) nationallicence IJzerman Adriaan Division of Medicinal Chemistry, Center for Bio-Pharmaceutical Sciences, P.O. Box 9502, NL-2300RA, Leiden, The Netherlands aut Kruidering Marieke Division of Medicinal Chemistry, Center for Bio-Pharmaceutical Sciences, P.O. Box 9502, NL-2300RA, Leiden, The Netherlands aut van Weert Anton Division of Medicinal Chemistry, Center for Bio-Pharmaceutical Sciences, P.O. Box 9502, NL-2300RA, Leiden, The Netherlands aut van Belle Herman Department of Biochemistry, Janssen Research Foundation, B-2340, Beerse, Belgium aut Janssen Cor Department of Metabolism and Pharmacokinetics, Janssen Research Foundation, B-2340, Beerse, Belgium aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/5(1992-05-01), 558-563 0028-1298 345:5<558 1992 345 210 https://doi.org/10.1007/BF00168949 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00168949 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- IJzerman Adriaan Division of Medicinal Chemistry, Center for Bio-Pharmaceutical Sciences, P.O. Box 9502, NL-2300RA, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Kruidering Marieke Division of Medicinal Chemistry, Center for Bio-Pharmaceutical Sciences, P.O. Box 9502, NL-2300RA, Leiden, The Netherlands aut NATIONALLICENCE 700 1- van Weert Anton Division of Medicinal Chemistry, Center for Bio-Pharmaceutical Sciences, P.O. Box 9502, NL-2300RA, Leiden, The Netherlands aut NATIONALLICENCE 700 1- van Belle Herman Department of Biochemistry, Janssen Research Foundation, B-2340, Beerse, Belgium aut NATIONALLICENCE 700 1- Janssen Cor Department of Metabolism and Pharmacokinetics, Janssen Research Foundation, B-2340, Beerse, Belgium aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/5(1992-05-01), 558-563 0028-1298 345:5<558 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer