135997-57-8Relevant academic research and scientific papers
Discovery of small-molecule interleukin-2 inhibitors from a DNA-encoded chemical library
Leimbacher, Markus,Zhang, Yixin,Mannocci, Luca,Stravs, Michael,Geppert, Tim,Scheuermann, Jcrg,Schneider, Gisbert,Neri, Dario
supporting information; experimental part, p. 7729 - 7737 (2012/09/07)
Libraries of chemical compounds individually coupled to encoding DNA tags (DNA-encoded chemical libraries) hold promise to facilitate exceptionally efficient ligand discovery. We constructed a high-quality DNAencoded chemical library comprising 30 000 drug-like compounds; this was screened in 170 different affinity capture experiments. High-throughput sequencing allowed the evaluation of 120 million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor-associated antigen carbonic anhydrase IX (CA IX) and the pro-inflammatory cytokine interleukin-2 (IL-2) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL-2 was confirmed by molecular docking. Our findings suggest that DNA-encoded chemical libraries allow the facile identification of drug-like ligands principally to any protein of choice, including molecules capable of disrupting high-affinity protein-protein interactions.
Site-specific incorporation of glycosylated serine and tyrosine derivatives into proteins
Fahmi, Nour Eddine,Dedkova, Larisa,Wang, Bixun,Golovine, Serguei,Hecht, Sidney M.
, p. 3586 - 3597 (2007/12/29)
Glycosylation of proteins can have a dramatic effect on their physical, chemical, and biological properties. Analogues of dihydrofolate reductase and firefly luciferase containing glycosylated amino acids at single, predetermined sites have been elaborate
Sequentially photocleavable protecting groups in solid-phase synthesis
Kessler, Martin,Glatthar, Ralf,Giese, Bernd,Bochet, Christian G.
, p. 1179 - 1181 (2007/10/03)
(Matrix presented) A sequential solid-phase peptide synthesis was developed using both photolabile linker and protecting groups. The chromatic sequential lability between a tert-butyl ketone-derived linker (sensitive to irradiation at 305 nm) and a nitroveratryloxycarbonyl (NVOC) group (sensitive at 360 nm) was exploited to prepare Leu-Enkephalin in a 55% overall yield. This new strategy allows the preparation of peptides in essentially neutral medium, by avoiding the use of common deprotection reagents such as trifluoroacetic acid or piperidine.
