4-amino-1-(2-deoxy-beta-D-ribofuranosyl)-6,7-dihydro-1H,5H-cyclopentapyrimidine-2-one

The crystal structure of C12H17N304 has been determined. This modified base is in a syn conformation with respect to the deoxyribose sugar, which adopts a distorted C3'/04'-endo pucker

4-Nitrophenyl activated esters are superior synthons for indirect radiofluorination of biomolecules

Indirect radiolabelling has for a long time been the mainstay strategy for radiofluorination of biomolecules. Acylation of biomolecules through the use of an 18F-labelled activated ester is a standard method for indirect radiolabelling. However, the preparation of 18F-labelled activated esters is typically a complex and multistep procedure. Herein, we describe the use of 4-nitrophenyl (PNP) activated esters to rapidly prepare 18F-labelled acylation synthons in one step. Furthermore, we present a comparative study of PNP activated esters and the commonly utilised 2,3,5,6-tetrafluorphenyl (TFP) activated esters under direct radiofluorination conditions and demonstrate their relative acylation behaviour. We demonstrate the superiority of PNP esters under direct radiofluorination conditions with favourable acylation kinetics

Automated preparation of clinical grade [Ga-68]Ga-DOTA-CP04, a cholecystokinin-2 receptor agonist, using iPHASE MultiSyn synthesis platform

BACKGROUND: Gallium-68 ([68Ga]Ga) labelled radiopharmaceuticals have become a valuable tool in clinical practice using Positron Emission Tomography (PET). These agents are typically produced on-site owing to the short half-life of [68Ga]Ga (68 min), which hinders distant transportation and often cannot comply with Good Manufacturing Practice (GMP) in hospital environments due to limited resources or infrastructure constraints. Moreover, full blown GMP production of radiopharmaceuticals under development can be prohibitively expensive. [68Ga]Ga-DOTA-CP04 is a promising peptide for imaging neuroendocrine tumors overexpressing the cholecyctokinin-2 receptor. Automation is an integral process in ensuring the radiopharmaceuticals produced under non-GMP conditions are of a uniform quality for routine clinical use. Herein, we describe the development of an automation platform, the iPHASE MultiSyn radiosynthesizer, to produce 68Ga-labelled DOTA-CP04 for routine clinical provision. RESULTS: The use of the MultiSyn module for 68Ga-labelling of DOTA-CP04 was investigated. [68Ga]Ga-DOTA-CP04, was reproducibly prepared in high (> 70%) decay-corrected yields. [68Ga]Ga-DOTA-CP04 passed all predetermined acceptance criteria for human injection. CONCLUSIONS: [68Ga]Ga-DOTA-CP04 was produced effectively using the MultiSyn module in a consistent and reproducible manner suitable for human injection

One‐step radiosynthesis of 4‐nitrophenyl 2‐[18F]fluoropropionate ([18F]NFP); improved preparation of radiolabeled peptides for PET imaging

The versatile 18F‐labeled prosthetic group, 4‐nitrophenyl 2‐[18F]fluoropropionate ([18F]NFP), was synthesized in a single step in 45 min from 4‐nitrophenyl 2‐bromopropionate, with a decay corrected radiochemical yield of 26.2% ± 2.2%. Employing this improved synthesis of [18F]NFP, [18F]GalactoRGD — the current ‘gold standard’ tracer for imaging the expression of αVβ3 integrin — was prepared with high specific activity in 90 min and 20% decay corrected radiochemical yield from [18F]fluoride. © 2013 John Wiley & Sons, Ltd

Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine.

We have attempted to alleviate the pH dependency of triplex recognition of guanine by using intermolecular triplexes containing 2-amino-5-(2-deoxy-d-ribofuranosyl)pyridine (AP) as an analogue of 2'-deoxycytidine (dC). We find that for the beta-anomer of AP, the complex between (AP)6T6and the target site G6A6*T6C6is stable, generating a clear DNase I footprint at oligonucleotide concentrations as low as 0.25 microM at pH 5.0, in contrast to 50 microM C6T6which has no effect on the cleavage pattern. This complex is still stable at pH 6.5 producing a footprint with 1 microM oligonucleotide. Oligonucleotides containing the alpha-anomer of AP are much less effective than the beta-anomer, though in some instances they are more stable than the unmodified oligonucleotides. The results of molecular dynamics studies on a range of AP-containing triplexes has rationalized the observed stability behaviour in terms of hydrogen-bonding behaviour

One-step radiosynthesis of 4-nitrophenyl 2-[F-18]fluoropropionate ([F-18]NFP); improved preparation of radiolabeled peptides for PET imaging

The versatile (18) F-labeled prosthetic group, 4-nitrophenyl 2-[(18) F]fluoropropionate ([(18) F]NFP), was synthesized in a single step in 45 min from 4-nitrophenyl 2-bromopropionate, with a decay corrected radiochemical yield of 26.2% ± 2.2%. Employing this improved synthesis of [(18) F]NFP, [(18) F]GalactoRGD - the current 'gold standard' tracer for imaging the expression of αV β3 integrin - was prepared with high specific activity in 90 min and 20% decay corrected radiochemical yield from [(18) F]fluoride