Chemical Description of Hematopoietic Growth Factors

CHEMICAL DESCRIPTION OF HEMATOPOIETIC GROWTH FACTORS

Hematopoietic growth factors are generally glycopro-teins, which can be distinguished by their amino acid sequence and glycosylation pattern (carbohydrate linkages). The recombinant HGFs, however, are not always glycoproteins. In spite of the lack of the carbohydrate moieties, they may still assume the structure necessary to exert the same biologic activity of the glycosylated form. In some cases, however, additional carbohydrates have been engineered and added to the native CSF to increase circulating half-life. Most HGFs are single-chain polypeptides. The carbohydrate content varies by growth factor and production method, which in turn affects the mole-cular weight but not necessarily the biologic activity.

Each HGF is encoded by a specific gene. Production of the recombinant proteins is accom-plished by first identifying the gene in question, isolating it by various techniques, inserting the gene of interest into a plasmid, and then expressing the protein of interest in a biologic system (e.g., bacteria, yeast, or mammalian cells) to produce recombinant growth factors.

The HGFs that will be discussed in detail include:

·        the white cell factors factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-

·         macrophage colony-stimulating factor (GM-CSF);

·          the red cell factors, the erythropoietins (EPO) and

·        darbepoetin alfa;

·        the platelet factors, thrombopoietin (TPO), mega-karyocyte growth and development factor (MGDF),

·         and interleukin-11 (IL-11); and

·          an early acting HGF, stem cell factor (SCF).

A summary of the HGFs and their activities is provided in Table 1.