Kinetics of the carbamylation of the amino groups of sickle cell hemoglobin by cyanate.

The NH2-terminal valine residues of both chains of oxyhemoglobin S are carbamylated 50 to 100 times faster at pH 7.4 than the a-NH2 groups of the lysine residues of the protein up to a level of 1 carbamyl group per hemoglobin molecule. The pseudo-first order rate constants for the carbamylation of the NHz-terminal residues of carbonmonoxyhemoglobins A and S are identical for the proteins either in the tetrameric state or as the p-hydroxymercuribenzoate derivatives of the individual chains. The rate constant for the carbamylation of deoxyhemoglobin A is the same as that for deoxyhemoglobin S, and the deoxyhemoglobins are carbamylated about twice as rapidly as the liganded proteins. These results indicate that the pK,, values of the NH&erminal valine residues of hemoglobins A and S are probably identical. Carbon dioxide competes for the site of the carbamylation with deoxyhemoglobin more effectively than it does with carbonmonoxyhemoglobin. Since O=C=O is known to bind preferentially to deoxyhemoglobin, these data provide experimental support for the suggestion that HN=C=O, the reactive tautomer of cyanate, is a structural analog of o==c=o.