N-acetylated sialic acids and related sialosides

Patent metadata

Field	Value
Publication number	US-12162901-B2
Application number	US-202117491518-A
Country	US
Kind code	B2
Filing date	Sep 30, 2021
Priority date	Nov 23, 2016
Publication date	Dec 10, 2024
Grant date	Dec 10, 2024

Abstract

The present invention provides N-acetyl derivatives of sialic acids, including N-acetyl derivatives of Neu5Ac and Neu5Gc. Methods for preparing related precursors and a variety of sialosides are also disclosed.

First claim

What is claimed is:

1. A compound according to Formula IVa:

wherein:
R 1 is —NHAc;
R 2 , R 3 , and R 4 are independently selected from the group consisting of —NHAc, —NH 2 , and —OH;
wherein at least one of R 2 , R 3 , and R 4 is —NHAc or —NH 2 ;
R 5 is selected from the group consisting of —NHR 5a , —OH, and —OAc;
R 5 ª is selected from the group consisting of Ac, Gc, GcAc, GcN 3 , GcNH 2 , GcNAc, and hydrogen;
Ac is —C(O)CH 3 ; Gc is —C(O)CH 2 OH; GcAc is —C(O)CH 2 OC(O)CH 3 ; GcN 3 is —C(O)CH 2 N 3 ; GcNH 2 is —C(O)CH 2 NH 2 ; GcNAc is —C(O)CH 2 NHC(O)CH 3 ; and
R 6 is selected from the group consisting of a galactoside, an N-acetylgalactosaminide, a glucoside, an N-acetylglucosaminide, and a sialoside.

2. The compound of claim 1 , wherein R 6 is present as a member of an oligosaccharide or a polysaccharide.

3. The compound of claim 1 , wherein at least one of R 2 , R 3 , and R 4 is —OH.

4. The compound of claim 3 , wherein R 5 is —NHR 5a .

5. The compound of claim 4 , wherein R 5a is Ac or Gc.

6. A method for sialylating a glycoprotein, a glycolipid, or a cell surface, the method comprising combining the glycoprotein, glycolipid or cell with a compound according to claim 5 under conditions sufficient to covalently bond the compound to the glycoprotein, glycolipid, or cell surface,
wherein combining the glycoprotein or glycolipid with the compound according to claim 5 comprises forming a mixture comprising the glycoprotein or glycolipid, the compound, and a sialyltransferase,
wherein combining the cell with the compound according to claim 5 comprises culturing the cell in the presence of the compound.

7. A compound according to Formula IVa:

wherein:
R 1 is —NHAc;
R 2 , R 3 , and R 4 are independently selected from the group consisting of —NHAc, —NH 2 , and —OH;
R 5 is selected from the group consisting of —NHR 5a , —OH, and —OAc;
R 5a is selected from the group consisting of Gc, GcAc, GcN 3 , GcNH 2 , GcNAc, and hydrogen;
Ac is —C(O)CH 3 ; Gc is —C(O)CH 2 OH; GcAc is —C(O)CH 2 OC(O)CH 3 ; GcN 3 is —C(O)CH 2 N 3 ; GcNH 2 is —C(O)CH 2 NH 2 ; GcNAc is —C(O)CH 2 NHC(O)CH 3 ; and
R 6 is selected from the group consisting of a galactoside, an N-acetylgalactosaminide, a glucoside, an N-acetylglucosaminide, and a sialoside.

8. A compound according to Formula IVa:

wherein:
R 1 is —OH;
R 2 , R 3 , and R 4 are independently selected from the group consisting of —NHAc, —NH 2 , and —OH;
R 5 is selected from the group consisting of —NHR 5a , —OH, and —OAc;
R 5a is selected from the group consisting of GcAc, GcN 3 , GcNH 2 , GcNAc, and hydrogen;
GcAc is —C(O)CH 2 OC(O)CH 3 ; GcN 3 is —C(O)CH 2 N 3 ; GcNH 2 is —C(O)CH 2 NH 2 ; GcNAc is —C(O)CH 2 NHC(O)CH 3 ; and
R 6 is selected from the group consisting of a galactoside, an N-acetylgalactosaminide, a glucoside, an N-acetylglucosaminide, and a sialoside.

Assignees

• Univ California

Inventors

• Chen Xi
• Xiao An
• Kooner Anoopjit
• Santra Abhishek
• Varki Ajit
• Yu Hai
• Wang Lee-Ping
• Li Wanqing

Classifications

• C12P19/64

  Preparation of S-glycosides, e.g. lincomycin · CPC title

• C12P19/44

  Preparation of O-glycosides, e.g. glucosides {(polysaccharides and not substituted disaccharides C12P19/04, C12P19/12)} · CPC title

• C12P19/28

  N-glycosides · CPC title

• C07H15/203

  Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems · CPC title

• C07H15/14

  attached to a sulfur, selenium or tellurium atom of a saccharide radical · CPC title