Compositions and methods for enforcing fucosylation of lactosaminyl glycans in human cells with alpha(1,3)-fucosyltransferases

Patent metadata

Field	Value
Publication number	US-11939616-B2
Application number	US-202017027794-A
Country	US
Kind code	B2
Filing date	Sep 22, 2020
Priority date	Mar 23, 2018
Publication date	Mar 26, 2024
Grant date	Mar 26, 2024

Abstract

The present disclosure provides, inter alia, compositions and methods for enforcing a pattern of cell surface fucosylated lactosaminyl glycans on a human cell. In certain embodiments, the compositions and/or methods utilize one or more members of the α(1,3)-fucosyltransferase family. In certain embodiments, a process for custom-modifying a fucosylated lactosaminyl glycan on a human cell is disclosed.

First claim

What is claimed is:

1. A process for custom engineering a fucosylated lactosaminyl glycan comprising:
(a) determining a desired enforced glycosylation pattern for a target human cell, wherein the enforced glycosylation pattern is selected from the group consisting of:
(i) sLe x (+)>>Le x (+), with Di-Fuc-sLe x (+), and VIM-2 (−); and
(ii) Le x (+), sLe x (−), VIM-2 (−), and Di-Fuc-sLe x (−);

(b) selecting an α(1,3)-fucosyltransferase VI capable of producing the desired glycosylation pattern; and
(c) contacting the target human cell with the selected α(1,3)-fucosyltransferase VI.

2. The process according to claim 1 , wherein contacting the human cell with Fucosyltransferase IV results in the enforced glycosylation pattern of (i).

3. A method for identifying a human cell via its glycosignature comprising the steps of:
(a) providing a population of human cells;
(b) contacting the population of human cells with an α(1,3)-fucosyltransferase VI;
(c) detecting fucosylated lactosaminyl glycans Le x , sLe x , VIM-2, and Di-Fuc-sLe x on the population of human cells of step (b); and
(d) identifying the population of human cells detected in step (c) having an enforced fucosylated lactosaminyl glycan pattern selected from the group consisting of:
(i) sLe x (+)>>Le x (+), with Di-Fuc-sLe x (+), and VIM-2 (−); and
(ii) Le x (+), sLe x (−), VIM-2 (−), and Di-Fuc-sLe x (−).

4. The method according to claim 3 , wherein contacting the cell with Fucosyltransferase VI results in the enforced glycosylation pattern of (i).

Assignees

• The Brigham And Womens Hospital
• Brigham & Womens Hospital Inc

Inventors

• Sackstein Robert

Classifications

• C12P21/005 Primary

  Glycopeptides, glycoproteins · CPC title

• C12Y204/01214

  Glycoprotein 3-alpha-L-fucosyltransferase (2.4.1.214) · CPC title

• C12Y204/01065

  3-Galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase (2.4.1.65), i.e. alpha-1-3 fucosyltransferase · CPC title

• C12Y204/01152

  4-Galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase (2.4.1.152) · CPC title