NON-HYPERTENSIVE PEGYLATED HEMOGLOBINS AND THEIR MANUFACTURING PROCESS

摘要

The present invention provides a hemoglobin molecule (Hb) having six ± one PEG chains, wherein two of said PEG chains are bound to Cys-93 (beta) of Hb, and the remaining PEG chains are bound to thiol groups introduced on epsilon-NH2 of Hb. The present invention also provides a process for preparing a modified hemoglobin molecule (Hb), comprising the steps of: (a) reacting Hb with 8-15 fold excess of iminothiolane to form thiolated Hb; and (b) reacting the thiolated Hb with 16-30 fold excess of PEG functionalized with a maleimide moiety, to form the modified Hb.