US 12,215,078 B2
Compositions and methods for protein labeling, modification, analysis, and targeted delivery
Sankaran Thayumanavan, Amherst, MA (US); Richard W. Vachet, Belchertown, MA (US); Jiaming Zhuang, Amherst, MA (US); and Bo Zhao, Sunderland, MA (US)
Assigned to University of Massachusetts, Boston, MA (US)
Appl. No. 17/254,433
Filed by University of Massachusetts, Boston, MA (US)
PCT Filed Jun. 28, 2019, PCT No. PCT/US2019/039697
§ 371(c)(1), (2) Date Dec. 21, 2020,
PCT Pub. No. WO2020/006340, PCT Pub. Date Jan. 2, 2020.
Claims priority of provisional application 62/823,447, filed on Mar. 25, 2019.
Claims priority of provisional application 62/691,248, filed on Jun. 28, 2018.
Prior Publication US 2021/0380635 A1, Dec. 9, 2021
Int. Cl. C07C 69/736 (2006.01); A61K 47/54 (2017.01); C07C 69/593 (2006.01); C07C 229/30 (2006.01); C07C 229/34 (2006.01); C07C 235/28 (2006.01); C07C 271/28 (2006.01); C07C 311/53 (2006.01); C07C 323/54 (2006.01); C07D 213/20 (2006.01); C07D 213/74 (2006.01); C07K 1/13 (2006.01)
CPC C07C 69/736 (2013.01) [A61K 47/54 (2017.08); C07C 69/593 (2013.01); C07C 229/30 (2013.01); C07C 229/34 (2013.01); C07C 235/28 (2013.01); C07C 271/28 (2013.01); C07C 311/53 (2013.01); C07C 323/54 (2013.01); C07D 213/20 (2013.01); C07D 213/74 (2013.01); C07K 1/13 (2013.01)] 8 Claims
 
1. A method for labeling a protein, comprising:
providing a protein of formula (IV) comprising a nucleophilic group (Nu) at a point of desired labeling:
R-Nu,  (IV)
wherein R-Nu is R—SH or R—NH2;
reacting the protein of formula (IV) with a compound of formula (V) having both a label and a reporter group:

OG Complex Work Unit Chemistry
wherein
R3 is H;
R4 is H;
Y is O;
L is a linking group comprising —(CH2CH2O)n—, wherein n is an integer from 1 to 10, and the reaction results in releasing of the reporter and formation of a labeled protein of formula (VI)

OG Complex Work Unit Chemistry
and
detecting a signal of the reporter and/or the presence of the label to analyze or quantify the protein.