219967-66-5Relevant academic research and scientific papers
A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids
Siciliano, Carlo,De Marco, Rosaria,Guidi, Ludovica Evelin,Spinella, Mariagiovanna,Liguori, Angelo
, p. 10575 - 10582 (2013/02/22)
The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.
Applying small molecule microarrays and resulting affinity probe cocktails for proteome profiling of mammalian cell lysates
Shi, Haibin,Uttamchandani, Mahesh,Yao, Shao Q.
, p. 2803 - 2815 (2012/07/14)
Small molecule microarrays (SMMs) are proving to be increasingly important tools for assessing protein-ligand interactions, as well as in screening for enzyme substrates and inhibitors, in a high-throughput manner. We previously described an SMM-facilitated screening strategy for the rapid identification of probes against γ-secretase, an aspartic protease. In this article, we extend upon this work with an expanded library of hydroxyethylamine-derived inhibitors which non-exclusively target aspartic proteases. Our library is diversified across P2, P1, P1 ′, and P2′ positions. Accordingly, 86 new inhibitors are synthesized using a combinatorial, solid-phase synthetic approach, bringing the total library size to 284-biotinylated compounds, which were arrayed onto avidin slides. In order to elucidate enzymatic activity and profiles within complex biological samples, screening is performed using fluorescently-labeled mammalian cell lysates. This yielded reproducible profiles or binding fingerprints that correspond with interactions from aspartic proteases or accessory proteins as well as other interacting targets that were present in the sample. The brightest microarray hits were converted to affinity-based probes (AfBPs) using convenient, 1-step "click" chemistry with benzophenone from the relevant building blocks. Pull-down/mass spectrometric analysis with these probes (individuals or cocktail) yielded putative protein targets that include well-known aspartic proteases, such as cathepsinD which is a clear marker for breast cancer cell lines, T47D. Many other hits were also identified, which may be secondary or tertiary interactors of aspartic proteases, or yet unreported off-targets of the hydroxyethylamine pharmacophore. Our work herein thus provides a candidate list of biomarkers for further investigations. Taken together, this SMM-facilitated strategy for the discovery of new AfBPs should provide a useful tool for high-throughput development of novel small molecule probes and the identification of new aspartic proteases as well as related biomarkers in the future.
Convenient and simple homologation of Nα-urethane protected α-amino acids to their β-homologues with concomitant o-nitrophenylesters formation
Ananda,Gopi,Suresh Babu
, p. 790 - 795 (2007/10/03)
The Wolff rearrangement of α-aminodiazoketones derived from Nα-urethane protected α-amino acids in presence of o-nitrophenol catalyzed by silver acetate at low temperature is described. The potential utility of the well-known ketene intermediat
(S)-β3-homolysine- and (S)-β3-homoserine-containing β-peptides: CD spectra in aqueous solution
Abele, Stefan,Guichard, Gilles,Seebach, Dieter
, p. 2141 - 2156 (2007/10/03)
For further structural studies and for physiological investigations of β-peptides, it is necessary to have H2O-soluble derivatives. Thus, we have prepared β-hexa-, β-hepta-, and β-nonapeptides (1-6) with two, three, and seven side chains of lys
