53-79-2Relevant articles and documents
Radiosynthesis of Carbon-11 Labeled Puromycin as a Potential PET Candidate for Imaging Protein Synthesis in Vivo
Milicevic Sephton, Selena,Aigbirhio, Franklin I.
, p. 647 - 651 (2016)
In order to address the limitations associated with the present range of PET radiotracers used for imaging protein synthesis in vivo we have synthesized a candidate PET radiotracer based on Puromycin (3, PURO), a protein synthesis inhibitor. The desmethylPURO 9 precursor for radiolabeling with carbon-11 radioisotope was synthesized in two steps employing EDC/HOBt amide coupling in overall 76% yield. Optimal conditions for radiolabeling were then established via methylation/deprotection sequence. Under these conditions as determined by NMR analysis 9 showed partial stability (ca. 80%) under acidic conditions. Limited evidence of stereochemical stability of 3 was also found. The radiolabeling of intermediate [11C]12 was accomplished with up to 57% conversion from [11C]iodomethane. An automated method was then developed for high radioactivity radiosynthesis to produce [11C]3 ([11C]PURO) in 16 ± 6% (n = 3) decay corrected radiochemical yields.
Design of photocaged puromycin for nascent polypeptide release and spatiotemporal monitoring of translation
Buhr, Florian,Kohl-Landgraf, J?rg,Tomdieck, Susanne,Hanus, Cyril,Chatterjee, Deep,Hegelein, Andreas,Schuman, Erin M.,Wachtveitl, Josef,Schwalbe, Harald
, p. 3717 - 3721 (2015/03/18)
The antibiotic puromycin, which inhibits protein translation, is used in a broad range of biochemical applications. The synthesis, characterization, and biological applications of NVOC-puromycin, a photocaged derivative that is activated by UV illumination, are presented. The caged compound had no effect either on prokaryotic or eukaryotic translation or on the viability of HEK 293 cells. Furthermore, no significant release of ribosome-bound polypeptide chains was detected invitro. Upon illumination, cytotoxic activity, invitro translation inhibition, and polypeptide release triggered by the uncaging of NVOC-puromycin were equivalent to those of the commercial compound. The quantum yield of photolysis was determined to be 1.1±0.2 % and the NVOC-puromycin was applied to the detection of newly translated proteins with remarkable spatiotemporal resolution by using two-photon laser excitation, puromycin immunohistochemistry, and imaging in rat hippocampal neurons. On like a light: The antibiotic puromycin (green) is a translation inhibitor that triggers the release of the nascent polypeptide chain (red) from the ribosome (yellow) and it is used in a number of applications. A photocaged puromycin derivative, NVOC-puromycin, was synthesized and characterized. Both functional recovery upon UV illumination and biological inactivity invitro and invivo were demonstrated.
Syntheses of puromycin from adenosine and 7-deazapuromycin from tubercidin, and biological comparisons of the 7-aza/deaza pair
Robins, Morris J.,Miles, Robert W.,Samano, Mirna C.,Kaspar, Roger L.
, p. 8204 - 8210 (2007/10/03)
Protection (05′) of 2′,3′-anhydroadenosine with tert-butyldiphenylsilyl chloride and epoxide opening with dimethylboron bromide gave the 3′-bromo-3′-deoxy xylo isomer which was treated with benzylisocyanate to give the 2′-O-(N-benzylcarbamoyl) derivative. Ring closure gave the oxazolidinone, and successive deprotection concluded an efficient route to 3′-amino-3′-deoxyadenosine. Analogous treatment ofthe antibiotic tubercidin {7-deazaadenosine; 4-amino-7-(β-D-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine} gave 3′-amino-3′-deoxytubercidin. Trifluoroacetylation of the 3′-amino function, elaboration of the heterocyclic amino group into a (1,2,4-triazol-4-yl) ring with N,N′-bis-[(dimethylamino)methylene]hydrazine, and nucleophilic aromatic substitution with dimethylamine gave puromycin aminonucleoside [9-(3-amino-3-deoxy-β-D-ribofuranosyl)-6-(dimethylamino)purine] and its 7-deaza analogue. Aminoacylation [BOC-(4-methoxy-L-phenylalanine)] and deprotection gave puromycin and 7-deazapuromycin. Most reactions gave high yields at or below ambient temperature. Equivalent inhibition of protein biosynthesis in a rabbit reticulocyte system and parallel growth inhibition of several bacteria were observed with the 7-aza/deaza pair. Replacement of N7 in the purine ring of puromycin by "CH" has no apparent effect on biological activity.