Synthesis of reagents for the one step incorporation of hydrazide functionality onto the lysine residues of proteins, and their use as linkers for carbonyl containing molecules

A photocleavable linker for the chemoselective functionalization of biomaterials

“…Gelatin from porcine skin (type B, 0.05 g) was dissolved in ultrapure water (10 mL, pH 4) and stirred for 48 hours at room temperature with the trifluoroacetate salt of 2,5-dioxopyrrolidin-1-yl-3-(4-hydrazinyl-4-oxobutanamido)propanoate (0.50 g), previously synthesized as described by Scott and Cwi. 31 The solution was then dialyzed for 72 hours against ultrapure water and lyophilized to yield gelatin hydrazide. To confirm the presence of the hydrazide functionality, the modified gelatin (10 mg) was treated with 4-hydroxybenzaldehyde (100 mg) in ultrapure water (5 mL; pH 5.5) for 18 hours at room temperature.…”

“…generating ''gelatin hydrazide'', we synthesized a short bifunctional linker containing a hydrazide trifluoroacetate salt at one end and an N-hydroxysuccinimide ester at the other. 31 Upon incubation with gelatin, free amine groups within the protein reacted with the NHS ester to form amide bonds, thus decorating the gelatin with pendant hydrazides (Fig. 6a).…”

Incorporation of Chemoselective Functionalities into Peptoids via Solid-Phase Submonomer Synthesis

“…Peptides containing a C-terminal hydrazide have been prepared by using an ester linkage to the solid support and cleaving the completed peptide chain by hydrazinolysis (40). Reagents have also been developed for converting lysine residues in peptides and proteins into hydrazide functionalities in aqueous solution (41), and in a scheme for the chemoselective acylation of 2-hydrazinylacetamide peptides a tris-Boc derivative of 2-hydrazinylacetic acid had to be prepared in order to avoid polymerization of 2-(2-tert-butoxycarbonylhydrazinyl)acetic acid during coupling (21).…”