Compounds and methods for selective c-terminal labeling

Patent metadata

Field	Value
Publication number	US-2023192761-A1
Application number	US-202217837360-A
Country	US
Kind code	A1
Filing date	Jun 10, 2022
Priority date	Jan 21, 2020
Publication date	Jun 22, 2023
Grant date	—

Abstract

The present disclosure relates to compounds and methods for selective C-terminal functionalization of peptides. In certain embodiments, the compounds have improved water-solubility, and are suitable for use in connection with peptide sequencing methodologies.

First claim

1 - 110 . (canceled)

111 . A compound of Formula (XV):

or a salt thereof, wherein
P is a peptide;
Y 2 comprises a moiety resulting from a click reaction with an azide group;
L 5 is a linker or is absent; and
Z 2 comprises one or more of polyethylene glycol, single-stranded DNA, double-stranded DNA, biotin, and streptavidin.

112 . The compound or salt of claim 111 , wherein Y 2 comprises a triazole.

113 . The compound or salt of claim 111 , wherein L 5 is a linker.

114 . The compound or salt of claim 113 , wherein the linker comprises a substituted or unsubstituted aliphatic chain, wherein one or more carbon atoms are optionally replaced by a heteroatom, an aryl, heteroaryl, cycloalkyl, or heterocyclyl moiety.

115 . The compound or salt of claim 113 , wherein the linker comprises polyethylene glycol (PEG).

116 . The compound or salt of claim 113 , wherein the linker comprises a peptide.

117 . The compound or salt of claim 111 , wherein Z 2 comprises polyethene glycol.

118 . The compound or salt of claim 111 , wherein Z 2 comprises single-stranded DNA.

119 . The compound or salt of claim 111 , wherein Z 2 comprises double-stranded DNA.

120 . The compound or salt of claim 111 , wherein Z 2 comprises biotin.

121 . The compound or salt of claim 111 , wherein Z 2 comprises streptavidin.

122 . The compound or salt of claim 111 , wherein P comprises 2-100 amino acid residues.

123 . The compound or salt of claim 111 , wherein P comprises 2-30 amino acid residues.

124 . A surface, on which the compound or salt of claim 111 is immobilized.

125 . The surface of claim 124 , wherein the surface is a chip.

126 . A method of selective N-functionalization of a peptide, comprising reacting a plurality of peptides of Formula (XI):

or a salt thereof, wherein each P independently is a peptide having an N-terminal amine, with a compound of Formula (XII):

under conditions comprising Cu 2+ , or a precursor thereof, and a buffer having a pH of 10-11; to obtain a plurality of ε-azido compounds of the Formula (XIIIb):

or a salt thereof.

127 . The method of claim 126 , further comprising reacting the plurality of compounds of Formula (XIIIb), or a salt thereof, with a compound of Formula (XIV):
R 6 -L 5 -Z 2    (XIV)
wherein R 6 is a moiety comprising an alkyne or a strained alkene;
L 5 is a linker or is absent; and
Z 2 comprises one or more of polyethylene glycol, single-stranded DNA, double-stranded DNA, biotin, and streptavidin;
to obtain a plurality of compounds of Formula (XV):

or a salt thereof, wherein Y 2 comprises a moiety resulting from a click reaction with the azide moiety of Formula (XIIIb), or a salt thereof, and R 6 .

Assignees

• Quantum Si Inc

Inventors

• Huang Haidong
• Nani Roger
• Ad Omer
• Reed Brian
• Dyer Matthew
• Boer Robert E

Classifications

• C07K1/128 Primary

  sequencing · CPC title

• C07K14/195

  from bacteria · CPC title

• C07K1/12

  by hydrolysis {, i.e. solvolysis in general} · CPC title

• C07K1/34

  by filtration, ultrafiltration or reverse osmosis · CPC title

• C07K1/1077 Primary

  by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids · CPC title