Amino groups reversible reductive alkylation

Figure 18. Reversible reductive alkylation of amino groups. Amino groups are alkylated first by treatment with (a) glycolaldehyde or (b) acetol in the presence of sodium borohydride. Reversal of the modification is effected by treating the modified amino group with 10-20mM NalOh for 30 min (85).

Aldehydes and ketones react reversibly with the amino groups of proteins to form aldimines or ketimines (Schiff bases),16 The SchifF base thus formed may be reduced with sodium borohydride, to afford alkylamines, which are stable. This reductive amination technique has been widely used for the alkylation of the 6-amino group of lysine.77... 

Reversible Modifications. Reversibility of a modification is frequently a desired characteristic in order to regain the protein in its original native form. A variety of methods (I) is available for this purpose. Sometimes a further intermediate modification is necessary as used recently in the reductive alkylation of amino groups with an a-hydroxy aldehyde or ketone and subsequent removal of the hydroxyalkyl group by periodate cleavage (85) (see Figure 18). 

A transition metal catalyst has also been used to effect the reductive alkylation of amino groups on proteins [41], This reaction uses [Cp Ir(4-4 -dimethoxybipy)(H20)]S04 31 as a mild transfer hydrogenation catalyst and formate ion as the stoichiometric hydride source, in Fig. 10.3-11 (a). Presumably, this reaction occurs via the reversible formation of imine 33 with free amino groups on the protein surface, followed by reduction of iridium hydride 32. For most proteins, multiple modifications are observed (Fig. 10.3-ll(b)), although the overall level of conversion can be altered through variation of either the reaction temperature or the concentrations of the aldehyde and catalyst. In general, the reaction has shown excellent reliability for protein alkylation between pH 5 and 7.4. 

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