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IOCB Prague

Synthesis of Radiolabeled Compounds

Aleš Marek Group
Service Group
CHEM cluster

About our group

Radioactive labels used for tracing of studied ligands have long been a part of the biochemical laboratory repertoire. Radioactivity gives a clear, unmistakable signal, and its use is fairly straightforward. We are devoted to supply radioactively labeled compounds to biochemical research teams of the institute, provide radiometric services, conduct radioactive waste management and supervise radiation safety rules within the institute.

GAMMA RAY EMITTER - 125I
We use optimized low-cost labeling procedure of peptides (up 70 amino acid residues) with IODO–GEN™– Na[125I] system. Produced are purified mono-iodinated peptides with specific activities over 2 000 Ci/mmol, separated from over-iodinated and starting peptides using radio-HPLC. Lyophilized 125I-labeled peptides can be stored at -20 °C for a long period of time.


β-PARTICLE EMITTER - 3H (14C)
Tritium/carbon-14 labeling of complex, multifunctional drug candidates requires mild, fast and safe preparative methods. We have expertise handling well-established methods used for introduction of tritium into biologically active molecules – from simple catalytic hydrogen isotope exchange through reduction of carbon-carbon multiple bonds, catalytic reductive dehalogenations to reductions with in-house synthesized carrier-free complex metallic tritides. We have been investigating the feasibility of Frustrated Lewis Pairs (FLP) as a mild catalysts for various tritiations in the quest for alternative orthogonal tritiation methods. The radiochemical purity of produced tracers is always checked by radio-HPLC, radio-TLC and 3H NMR spectra.

Publications

All publications
Development of a human vasopressin V<sub>1a</sub>-receptor antagonist from an evolutionary-related insect neuropeptide
Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide
M. G. Di Giglio
M. Muttenthaler
K. Harpsoe
Z. Liutkeviciute
P. Keov
T. Eder
T. Rattei
S. Arrowsmith
S. Wray
Aleš Marek
Tomáš Elbert
P. F. Alewood
D. E. Gloriam
C. W. Gruber
Scientific Reports 7 : 41002 (2017).
Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.
Immunoaffinity chromatography combined with tandem mass spectrometry: A new tool for the selective capture and analysis of brassinosteroid plant hormones
Jana Oklešťková
Danuše Tarkowská
L. Eyer
Tomáš Elbert
Aleš Marek
Z. Smržová
Ondřej Novák
M. Franěk
V.N. Zhabinskii
Miroslav Strnad
Talanta 170 (1): 432-440 (2017).
Diversity-Oriented Peptide Stapling: A Third Generation Copper-Catalysed Azide-Alkyne Cycloaddition Stapling and Functionalisation Strategy
P. T. Tran
C. O. Larsen
T. Rondbjerg
M. De Foresta
M. B. A. Kunze
Aleš Marek
J. H. Loper
L.-E. Boyhus
A. Knuhtsen
K. Lindorff-Larsen
D. S. Pedersen
Chemistry - A European Journal 23 (14): 3490-3495 (2017).