32775-08-9

Upstream product

• 4792-15-8 Pentaethylene glycol 
• 132684-09-4 di-tert-butyl 3,6,9,12-tetraoxatetradecanedioate 
• 112-27-6 2,2'-[1,2-ethanediylbis(oxy)]bisethanol 

Downstream Products

• 1412423-19-8 C₇₈H₁₀₈N₁₀O₁₆ 
• 84293-33-4 (S)-2-{2-[2-(2-{2-[((S)-1-Carboxy-2-phenyl-ethylcarbamoyl)-methoxy]-ethoxy}-ethoxy)-ethoxy]-acetylamino}-3-phenyl-propionic acid 
• 84293-35-6 (S)-2-{2-[2-(2-{2-[((S)-1-Benzyloxycarbonyl-2-phenyl-ethylcarbamoyl)-methoxy]-ethoxy}-ethoxy)-ethoxy]-acetylamino}-3-phenyl-propionic acid benzyl ester 
• 145058-24-8 N,N-Dibenzyl-2-[2-(2-{2-[(dibenzylcarbamoyl)-methoxy]-ethoxy}-ethoxy)-ethoxy]-acetamide 

Relevant academic research and scientific papers

GPER PROTEOLYTIC TARGETING CHIMERAS

A molecule comprising a G-protein coupled estrogen receptor (GPER) ligand coupled to a linker coupled to an E3 ubiquitin ligase ligand and methods of using the molecule are provided. In one embodiment, the GPER ligand is estradiol and the E3 ubiquitin lig

SMALL MOLECULES

Compounds having the general structure A - L - B are presented wherein A and B are independently an E3 ubiquitin ligase protein binding ligand compound of formula 1A or 1 B. Pharmaceutical compositions comprising these compounds and methods of use are also presented.

Homo-PROTACs: Bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

E3 ubiquitin ligases are key enzymes within the ubiquitin proteasome system which catalyze the ubiquitination of proteins, targeting them for proteasomal degradation. E3 ligases are gaining importance as targets to small molecules, both for direct inhibition and to be hijacked to induce the degradation of non-native neo-substrates using bivalent compounds known as PROTACs (for 'proteolysis-targeting chimeras'). We describe Homo-PROTACs as an approach to dimerize an E3 ligase to trigger its suicide-type chemical knockdown inside cells. We provide proof-of-concept of Homo-PROTACs using diverse molecules composed of two instances of a ligand for the von Hippel-Lindau (VHL) E3 ligase. The most active compound, CM11, dimerizes VHL with high avidity in vitro and induces potent, rapid and proteasome-dependent self-degradation of VHL in different cell lines, in a highly isoform-selective fashion and without triggering a hypoxic response. This approach offers a novel chemical probe for selective VHL knockdown, and demonstrates the potential for a new modality of chemical intervention on E3 ligases.

Ligand Recognition by E- and P-Selectin: Chemoenzymatic Synthesis and Inhibitory Activity of Bivalent Sialyl Lewis x Derivatives and Sialyl Lewis x Carboxylic Acids

Described is the preparation of five sLex dimers and five sLex carboxylic acids by coupling chemoenzymatically synthesized amino-substituted sialyl Lewis x (sLex) derivative 4 to homobifunctional cross-linkers 20-24 of varying chain length. 20-24 were obtained by alkylating low-molecular-weight oligoethylene glycols with tert-butyl bromoacetate and subsequent transformation of the di-tert-butyl esters into disuccinimide esters. The products were assayed for inhibition against binding of a sLea-polymer to immobilized E- and P-selectin. In the E-selectin assay all dimers had lower IC50 values than the sLex monomer. The results show that comparable binding enhancements can be obtained with linkers of completely different length and rigidity. In the P-selectin assay four of the five sLex carboxylic acids displayed significantly improved inhibitory potency. The lowest IC50 value was observed for the compound with the shortest spacer between the sLex moiety and the additional carboxylate, being ca. 20-40 times more potent than unmodified sLex. These findings should be of importance for the design of new multivalent forms of sLex as well as sLex mimetics as high-affinity selectin ligands.

Enhancing the binding properties of a conformationally rigid podand ionophore

Stereospecific functionalization of a conformationally rigid podand yields new ionophores having binding properties comparable to those of the macrocyclic crown ethers.

CHIRAL AMINOACID CONTAINING ACYCLIC LIGANDS-I. SYNTHESES AND CONFORMATIONS

Synthesis and spectral properties of optically active acyclic ligands, containing two (S)-phenylalanine residues (3a-f) are described.The synthesis is achieved by two different routes.Conformational studies in different solvents are performed by dilution and temperature-dependent experiments of 1H and 13C NMR spectroscopy.