Site-specific chemoenzymatic protein modifications
AssigneeNovartis AG
InventorsAimee Richardson USERA, Zachary Hayes ROBINSON, Jennifer Stroka COBB
Life of this patent
Estimating the term…
Abstract
The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.
Claims11
1-97. (canceled)
A conjugate comprising a protein that has at least one lysine residue and is conjugated to a compound of the formula R1-(Leu)x-Gln-(Gly)y-(A-W—B—R2)z via a reaction of the at least one lysine residue with the Gln residue of the compound, wherein
- x is 0 or 1;
- y is 0 or 1;
- z is 0 or 1;
- R1 is
- W is selected from C1-C6 linear or branched alkyl or polyethylene glycol having a molecular weight of between about 40 and about 80,000 amu;
- A is absent or selected from —O—, —NH—, and —S—;
- B is absent or selected from —O—, —C(O)—, —NH—, —C(O)NH—, —NHC(O)—, —NHC(O)O—, —OC(O)NH—, —OC(O)O—, —C═N(OH)—, —S(O2)—, —NHS(O2)—, —S(O2)NH—, —S(O)—, —NHS(O)—, —S(O)NH—:
- —C(O)O—, —OC(O)—, —S—, ═NH—O—, ═NH—NH— and ═NH—N(C1-C20alkyl)-;
- and
- R2 is selected from a fatty acid, linear or branched C1-C3 alkyl-N3, cyclooctynyl, polysaccharide, —CH(OCH3)2,
- wherein each n is an integer independently selected from 0 to 6p and each n is selected from H and —NO2.
(canceled)
A conjugate comprising a protein that has at least one lysine residue and is conjugated to a compound selected from:
- wherein m is an integer selected from 1 to 2, n is an integer independently selected from 1 to 3, and q is an integer selected from 15 to 20 and wherein the conjugation is via a reaction of the at least one lysine residue with the Gln residue of the compound.
A conjugate comprising a protein that has at least one lysine residue and is conjugated to a compound of the formula R1-(Leu)x-Gln-(Gly)y-(A-W—B—R2)z via a reaction of the at least one lysine residue with the Gln residue of the compound, wherein
- x is 0 or 1;
- y is 0 or 1;
- z is or 1;
- R1 is
- W is polyethylene glycol having a molecular weight of between about 40 and about 80,000 amu;
- A is absent or selected from —O—, —NH—, and —S—;
- B is absent or selected from —O—, —C(O)—, —NH—, —C(O)NH—, —NHC(O)—, —NHC(O)O—, —OC(O)NH—, —OC(O)O—, —C═N(OH)—, —S(O2)-, —NHS(O2)—, —S(O2)NH—, —S(O)—, —NHS(O)—, —S(O)NH—;
- —C(O)O—, —OC(O)—, —S—, ═NH—O—, ═NH—NH— and ═NH—N(C1-C20alkyl)-;
- and
- R2 is a fluorophore.
Dependencies are inferred from the claim text.