ABSTRACT

Hematopoiesis, the process of blood cell production, is an enormous undertaking. This chapter provides an overview of the biology, biochemistry, and pharmacology of the colony-stimulating factors (CSFs) in order to better understand their use as therapeutic proteins, and to provide the basis for more recent studies of the structure-function relationships of these clinically valuable proteins. Colony-stimulating activity was operationally first defined as a substance(s) which sup ported the clonal growth of blood cells from their progenitors in semisolid cultures. Large amounts of purified recombinant CSFs are available by the methods of recombinant DNA technology. Several groups have investigated the functional role of carbohydrate modification of the CSFs. The chapter presents a discussion of potential routes to realize the goals will be presented to illustrate some of the directions presently being pursued towards the rational drug design of the CSFs. Polyethylene glycol (PEG) modification of proteins has long been known to increase the residence time of proteins in the vascular compartment.