Carbohydrate periodate oxidation

Starting from the appropriately substituted carbohydrates (e.g., II), 1,5-dialdehydcs are obtained by periodate oxidation. Subsequent double Henry reaction33 with nitromethane furnishes a variety of nitro-substituted carbohydrate derivatives. In most cases pure stereoisomers are obtained by crystallization of the reaction mixture3. 

Periodate Oxidation, Acid Hydrolysis, and Structure-Activity Relationships of Human Pituitary, Follicle-Stimulating Hormone, and Human Chorionic Gonadotrophin, J. F. Kennedy, M. F. Chaplin, and M. Stacey, Carbohydr. Res. 36 (1974) 369-377. 

The oxidative cleavage of v/c-diols to give two carbonyl functions (Eq. 5.3) by periodates was first observed by Malaprade and has since been widely applied to the carbohydrate area.50 Since both the reagent sodium periodate and the carbohydrate substrate are water soluble, the reaction is usually carried out in aqueous media.51 The reaction has been applied to polysaccharides such as starch.52 The periodate oxidations of sodium alginate in water as well as a dispersion in 1 1 ethanol-water mixture have been compared.53 Because sodium alginate forms a highly viscous solution, the oxidation was observed to be more extensive in ethanol-water. 

The carbonyl-reactive group on these crosslinkers is a hydrazide that can form hydrazone bonds with aldehyde residues. To utilize this functional group with carbohydrate-containing molecules, the sugars first must be mildly oxidized to contain aldehyde groups by treatment with sodium periodate. Oxidation with this compound will cleave adjacent carbon-carbon bonds which possess hydroxyl groups, as are abundant in polysaccharide molecules (Chapter 1, Sections 2 and 4.4). 

Figure 5.12 MPBH reacts with sulfhydryl-containing molecules through its maleimide end to produce thioether linkages. Its hydrazide group then can be used to conjugate with carbonyl-containing molecules (such as periodate-oxidized carbohydrates that contain aldehydes) to give hydrazone bonds.

Figure 9.26 AMCA-hydrazide can be used to label aldehyde-containing molecules, such as periodate-oxidized carbohydrates.

The hydrazide derivative of AMCA can be used to modify aldehyde- or ketone-containing molecules, including cytosine residues using the bisulfite activation procedure described in Chapter 27, Section 2.1. AMCA-hydrazide reacts with these target groups to form hydrazone bonds (Figure 9.26). Carbohydrates and glycoconjugates can be labeled specifically at their polysaccharide portion if the required aldehydes are first formed by periodate oxidation or another such method (Chapter 1, Section 4.4). 

The following protocol describes the use of biotin-hydrazide to label glycosylated proteins at their carbohydrate residues. Control of the periodate oxidation level can result in specific labeling of sialic acid groups or general sugar residues (Chapter 1, Section 4.4). 

Figure 14.19 Aldehyde-containing molecules, such as periodate-oxidized carbohydrates or glycoproteins, can be coupled to hydrazide-particles to form a hydrazone bond. This bond can be further stabilized by reduction...

Figure 18.19 Biotin-PEG4-hydrazide is a hydrophilic biotinylation reagent that can be used to modify glycans or carbohydrates at their reducing end or after periodate oxidation to create aldehydes.

Figure 20.14 Periodate oxidation of HRP creates aldehyde groups on the carbohydrate chains of the enzyme. Reaction with a Fab fragment then may be done using reductive amination to produce a lower-molecular-weight complex than would be obtained using intact IgG antibodies.

Hydrazide groups can react with carbonyl groups to form stable hydrazone linkages. Derivatives of proteins formed from the reaction of their carboxylate side chains with adipic acid dihydrazide (Chapter 4, Section 8.1) and the water-soluble carbodiimide EDC (Chapter 3, Section 1.1) create activated proteins that can covalently bind to formyl residues. Hydrazide-modified enzymes prepared in this manner can bind specifically to aldehyde groups formed by mild periodate oxidation of carbohydrates (Chapter 1, Section 4.4). These reagents can be used in assay systems to detect or measure glycoproteins in cells, tissue sections, or blots (Gershoni et al., 1985). 

Bobbitt, J.M. (1956) Periodate oxidation of carbohydrates. Adv. Carbohydr. Chem. 11, 1-41. 

Woodward, M.P., Young, W.W., and Bloodgood, R.A. (1985) Detection of monoclonal antibodies specific for carbohydrate epitopes using periodate oxidation./. Immunol. Meth. 78, 143-153. 

---