US 12,428,459 B2
Protein tag to induce ligand dependent degradation of protein/protein-fusions
Eric S. Fischer, Chestnut Hill, MA (US); Shourya Sonkar Roy Burman, Brookline, MA (US); Tyler Faust, Brookline, MA (US); Hojong Yoon, Cambridge, MA (US); and Radoslaw P. Nowak, Boston, MA (US)
Assigned to DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
Appl. No. 17/642,874
Filed by DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
PCT Filed Sep. 17, 2020, PCT No. PCT/US2020/051156
§ 371(c)(1), (2) Date Mar. 14, 2022,
PCT Pub. No. WO2021/055530, PCT Pub. Date Mar. 25, 2021.
Claims priority of provisional application 62/902,275, filed on Sep. 18, 2019.
Prior Publication US 2022/0402981 A1, Dec. 22, 2022
Int. Cl. C07K 14/47 (2006.01); C12N 15/62 (2006.01)
CPC C07K 14/4702 (2013.01) [C12N 15/62 (2013.01); C07K 2319/85 (2013.01); C07K 2319/95 (2013.01)] 27 Claims
 
1. A degron tag comprising a polypeptide which is a variant of ribonucleic acid (RNA) recognition motif (RRM), wherein in the presence of an aryl sulfonamide, the variant of RRM, is selectively bound and targeted for degradation by E3 ubiquitin ligase Cullin Really Interesting New Gene (RING) ligase 4 (CRL4) deoxyribonucleic acid (DNA) damage binding protein 1 (DDB 1) and Cullin-4 (CUL4) associated factor 15 (DCAF15) (CRL4DCAF15) wherein the presence of an aryl sulfonamide leads to degradation of the variant of RRM mediated by CRL4DCAF15 that is 2-100 fold greater than degradation of the wild-type RRM or RRM-containing protein mediated by CRL4DCAF15 wherein the variant of RRM differs from wild-type RRM or an RRM present in an RRM-containing protein by comprising an amino acid substitution at H258, S285, T287, K306, Q310, or E315, or a combination of two or more thereof, said amino acid substitution numbered in accordance with SEQ ID NO: 1, and wherein the amino acid substitution at K306 comprises K306E, K306L, K306T, or K306A.