Skip to Content
Merck
  • Destruction of DNA-Binding Proteins by Programmable Oligonucleotide PROTAC (O'PROTAC): Effective Targeting of LEF1 and ERG.

Destruction of DNA-Binding Proteins by Programmable Oligonucleotide PROTAC (O'PROTAC): Effective Targeting of LEF1 and ERG.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2021-08-17)
Jingwei Shao, Yuqian Yan, Donglin Ding, Dejie Wang, Yundong He, Yunqian Pan, Wei Yan, Anupreet Kharbanda, Hong-Yu Li, Haojie Huang
ABSTRACT

DNA-binding proteins, including transcription factors (TFs), play essential roles in various cellular processes and pathogenesis of diseases, deeming to be potential therapeutic targets. However, these proteins are generally considered undruggable as they lack an enzymatic catalytic site or a ligand-binding pocket. Proteolysis-targeting chimera (PROTAC) technology has been developed by engineering a bifunctional molecule chimera to bring a protein of interest (POI) to the proximity of an E3 ubiquitin ligase, thus inducing the ubiquitination of POI and further degradation through the proteasome pathway. Here, the development of oligonucleotide-based PROTAC (O'PROTACs), a class of noncanonical PROTACs in which a TF-recognizing double-stranded oligonucleotide is incorporated as a binding moiety of POI is reported. It is demonstrated that O'PROTACs of lymphoid enhancer-binding factor 1 (LEF1) and ETS-related gene (ERG), two highly cancer-related transcription factors, successfully promote degradation of these proteins, impede their transcriptional activity, and inhibit cancer cell growth in vitro and in vivo. The programmable nature of O'PROTACs indicates that this approach is also applicable to destruct other TFs. O'PROTACs not only can serve as a research tool but also can be harnessed as a therapeutic arsenal to target DNA binding proteins for effective treatment of diseases such as cancer.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
VH 032 amide-PEG2-acid, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
3-[1,3-Dihydro-4-(4-hydroxy-1-butyn-1-yl)-1-oxo-2H-isoindol-2-yl]-2,6-piperidinedione, ≥95.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
VH 032 amide-alkyl C3-acid, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
3-(3-Fluoro-4-piperidin-4-ylphenylamino)piperidine-2,6-dione hydrochloride, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
2,6-Piperidinedione, 3-[(3-aminophenyl)amino] hydrochloride, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pentanoic acid, 5-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]-, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-piperazine-acetic acid, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-PEG2-phosphoramidite
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-PEG1-C2-azide, ≥95.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
7-Octynoic acid, 8-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1-oxo-1H-isoindol-4-yl], ≥95.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
1H-Isoindole-1,3(2H)-dione, 2-(2,6-dioxo-3-piperidinyl)-5-(4-piperidinyloxy) hydrochloride, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-PEG2-C2-NH2 hydrochloride, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
3-[1,3-Dihydro-4-(5-hydroxy-1-pentyn-1-yl)-1-oxo-2H-isoindol-2-yl]-2,6-piperidinedione, ≥95.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide 4′-PEG3-amine hydrochloride, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
4-Aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
VH 032 amide-PEG3-acid, ≥95.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
VH032-OH, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-PEG2-C2-azide, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
(S,R,S)-AHPC-C5-phosphoramidite
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
(S,R,S)-AHPC-CO-PEG4-C2-acid, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
VH 032 amide-alkyl C5-acid, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-C5-phosphoramidite
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-piperazine-propanoic acid, ≥95.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-PEG3-OH, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
(S,R,S)-AHPC-CO-PEG1-C2-acid, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-piperidine-carboxylic acid, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
(S,R,S)-AHPC-Me-C5-COOH, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Pomalidomide-C2-NH2 hydrochloride, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
4-Pentynoic acid, 5-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1-oxo-1H-isoindol-4-yl], ≥95.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
VH032-cyclopropane-F, ≥95%
SKU
Pack Size
Availability
Price
Quantity