215168-72-2

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 178445-80-2 (E)-1-(3,4-dimethoxyphenyl)-3-(3-hydroxyphenyl)prop-2-en-1-one 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 121-71-1 3-Hydroxyacetophenone 
• 39684-80-5 2-(tert-butoxycarbonylamino)ethyl bromide 
• 178445-83-5 3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-1-propanone 

Downstream Products

• 1356846-23-5 C₅₈H₇₂N₄O₁₄S 
• 1356846-35-9 C₃₉H₄₇ClN₂O₁₀S 
• 215168-84-6 (1R)-1-[3-[2-[N-(tert-butoxycarbonyl)ethanamine]phenoxy-3-(3,4-dimethoxyphenyl)-1-propanyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-piperidinecarboxylate 
• 215168-73-3 (R)-N-(tert-butoxycarbonyl)-2-[3-[1-hydroxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]ethylamine 

Relevant academic research and scientific papers

Native FKBP12 engineering by ligand-directed tosyl chemistry: Labeling properties and application to photo-cross-linking of protein complexes in vitro and in living cells

The ability to modify target "native" (endogenous) proteins selectively in living cells with synthetic molecules should provide powerful tools for chemical biology. To this end, we recently developed a novel protein labeling technique termed ligand-directed tosyl (LDT) chemistry. This method uses labeling reagents in which a protein ligand and a synthetic probe are connected by a tosylate ester group. We previously demonstrated its applicability to the selective chemical labeling of several native proteins in living cells and mice. However, many fundamental features of this chemistry remain to be studied. In this work, we investigated the relationship between the LDT reagent structure and labeling properties by using native FK506-binding protein 12 (FKBP12) as a target protein. In vitro experiments revealed that the length and rigidity of the spacer structure linking the protein ligand and the tosylate group have significant effects on the overall labeling yield and labeling site. In addition to histidine, which we reported previously, tyrosine and glutamate residues were identified as amino acids that are modified by LDT-mediated labeling. Through the screening of various spacer structures, piperazine was found to be optimal for FKBP12 labeling in terms of labeling efficiency and site specificity. Using a piperazine-based LDT reagent containing a photoreactive probe, we successfully demonstrated the labeling and UV-induced covalent cross-linking of FKBP12 and its interacting proteins in vitro and in living cells. This study not only furthers our understanding of the basic reaction properties of LDT chemistry but also extends the applicability of this method to the investigation of biological processes in mammalian cells.

PROTEASE INHIBITORS

Compounds useful as protease inhibitors are provided, as are methods of use and preparation of such compounds and compositions containing such compounds. In one embodiment, the compounds are useful for inhibiting HIV protease enzymes, and are therefore useful in slowing the proliferation of HIV.

Synthesis and activity of bivalent FKBP12 ligands for the regulated dimerization of proteins

The total synthesis and in vitro activities of a series of chemical inducers of dimerization (CIDs) is described. The use of small-molecule CIDs to control the dimerization of engineered FKBP12-containing fusion proteins has been demonstrated to have broad utility in biological research as well as potential medical applications in gene and cell therapies. The facility and flexibility of preparation make this new class of wholly synthetic compounds exceptionally versatile tools for the study of intracellular signaling events mediated by protein-protein interactions or protein localization. While some congeners possess potency comparable to or better than the first generation natural product-derived CID, FK1012, structure-activity relationships are complex and underscore the need for application-specific compound optimizations. Copyright (C) 1998 Elsevier Science Ltd.