A Terminal Peptide Sequence of Human Hæmoglobin?

Abstract

IT was reported recently^1,2,3 that the chemical difference between the normal human hæmoglobin A and the abnormal hæmoglobins S and C resides in a tryptic peptide, called peptide 4, to which the following structure was assigned: histidyl-valyl-leucyl-leucyl-threonyl-prolyl-glutamyl-glutamyl-lysine. In hæmoglobins S and C the glutamic acid residue which is in italics is replaced by a valine and a lysine residue, respectively. Although the evidence available at the time of publication made the above structure appear likely, repeated attempts to confirm it by the Edman stepwise degradation method⁴ have not agreed with this formulation. We now wish to report that the sequence of peptide 4 in the hæmoglobins A and C is as indicated in Table 1, with histidine in position 2 and valine as the N-terminal amino-acid. Furthermore, this peptide is likely to be N-terminal in one of the hæmoglobin chains. The structure of peptide 4 from hæmoglobin S is still under investigation, but it seems likely—especially in the light of the work of Hill and Schwartz (following communication) that its structure is as shown. It should be noted that the sequence around the amino-acid which changes and the changes themselves in these mutational alterations are not affected by the new structure.