193148-58-2Relevant articles and documents
Efficient and direct solid phase synthesis of ketomethylenimino and ketomethylenamino peptides
Bernard, Elise,Vanderesse, Régis
, p. 8603 - 8606 (2004)
The reaction between the free amino terminus of a solid-supported peptide and a glyoxal leads to two families of pseudopeptides, the ketomethylenimino and the ketomethylenamino peptides. The aim of this study is the synthesis of pseudopeptides on solid supports, in order to quickly obtain modified peptides. We report a convenient step-by-step synthesis of ketomethylenimino ψ[CO-CH=N] and ketomethylenamino ψ[CO-CH2-NH] peptides. The key is the reaction between the free amino terminus of the supported peptide and a glyoxal-modified amino acid, leading to a ketomethylenimino bond, which can be reduced to a ketomethylenamino bond.
TUBULYSIN DERIVATIVES AND METHODS FOR PREPARING THE SAME
-
Page/Page column 21, (2020/02/16)
The invention relates to novel means and methods for the synthesis of tubulysin and derivatives thereof, which find their use e.g. as cytotoxic agents in targeted drug delivery. Provided is a method for preparing a tubulysin derivative, comprising reacting compounds A, B and C in a 3- component Passerini reaction, wherein compound A is a carboxylic acid according to the general formula (A); wherein compound B is an aldehyde according to the general formula (B); and wherein compound C is an isocyanide according to the general formula (C).
Applying small molecule microarrays and resulting affinity probe cocktails for proteome profiling of mammalian cell lysates
Shi, Haibin,Uttamchandani, Mahesh,Yao, Shao Q.
supporting information; experimental part, 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.