Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent.

The 11 C-labeled sulfonylurea receptor 1 (SUR1) ligand (S)-2-(( 11 C)methoxy)-4-(3-methyl-1-(2-piperidine-1-yl-phenyl)- butyl-carbamoyl)-benzoic acid (( 11 C)methoxy-repaglinide) was synthesized in an overall radiochemical yield of 35% after 55 min with a radiochemical purity higher than 99%. This compound is considered for the noninvasive investigation of the SUR1 receptor status of pancreatic b-cells by positron emission tomography (PET) in the context of type 1 and type 2 diabetes. The specific activity was 40-70 GBq/lmol. In vitro testing of the nonradioactive methoxy-repaglinide was performed to characterize the affinity for binding to the human SUR1 isoform. Methoxy-repaglinide induce…

Application of tris-allyl-DOTA in the preparation of DOTA–peptide conjugates

Abstract The synthesis of tris-allyl-DOTA starting from cyclen and its application in the preparation of DOTA–peptide conjugates is reported. Clinically important conjugates such as DOTA–Tyr3-octreotide (DOTA–TOC), DOTA–Tyr3-octreotate (DOTA–TATE) as well as a DOTA–RGD peptide were synthesized in high yields with Fmoc solid phase peptide synthesis. The final, extremely reliable de-allylation was achieved on solid phase by different methods identifying morpholine/Pd(0) as the most suitable one obtaining all DOTA peptide conjugates in high yields. All DOTA–peptides were purified by reversed phase HPLC and structural identity was proved using MALDI-TOF mass spectrometry.

Synthesis of a Tyr3-octreotate conjugated closo-carborane [HC2B10H10]: a potential compound for boron neutron capture therapy

Abstract A novel Tyr 3 -octreotate conjugated closo -carborane as a potential compound for boron neutron capture therapy was obtained via Fmoc solid phase peptide synthesis. The boron cluster [C 2 B 10 H 11 ] was introduced through the reaction of 6,9-bis(acetonitrile)decaborane and 5-hexynoic acid yielding a new closo -carborane conjugated carboxylic acid which was coupled subsequently with solid phase conjugated Tyr 3 -octreotate. The final boron-containing peptide was purified by preparative reverse phase HPLC and structural identity was proved applying MALDI-TOF mass spectrometry.

Synthesis and in vitro Evaluation of (S)-2-([11C]Methoxy)-4- [3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic Acid ([11C]Methoxy-repaglinide): A Potential ?-Cell Imaging Agent.

Synthesis and in Vitro Evaluation of Biotinylated RG108:  A High Affinity Compound for Studying Binding Interactions with Human DNA Methyltransferases

Small-molecule inhibitors of DNA methyltransferases such as RG108 represent promising candidates for cancer drug development. We report the synthesis and in vitro analysis of a biotinylated RG108 conjugate, 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(5-[3-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)pentanoylamino]propoxy]-1H-indol-3-yl)propionic acid (bio-RG108), for the evaluation of interactions with DNA methyltransferase enzymes. The structural design of the chemically modified inhibitor was aided by molecular modeling, which suggested the possibility for extensive chemical modifications at the 5-position of the tryptophan moiety in RG108. The inhibitory activity of the corresponding d…