Transferrins

As an alternative to targeting brain tumours which express the TfR, the transferrin approach can be used for the delivery of fusion proteins which bind to pharmacological receptors inside the central nervous system. An example of this is the construct consisting of nerve growth factor (NGF) and transferrin described in Section 11.8.2.3. The transferrin moiety in this type of construct will enable it to enter the brain, upon which the drug moiety will act by binding to its receptor. This approach seems especially suitable for compounds that cannot pass the blood-brain barrier, such as peptides and other hydrophilic substances. 

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Transferrin is essential for movement of iron and without it, as in genetic absence of transferrin, iron overload occurs in tissues. This hereditary atransferrinemia is coupled with iron-deficiency anemia. The iron overload in hereditary or acquired hemochromatosis results in fully saturated transferrin and is treated by phlebotomy (10). 

Three forms of folate appear to be transported ia the blood foHc acid, folate loosely bouad to low affinity binder semm proteins (such as albumin, a-macroglobulin, and transferrin), and folate bound to high affinity protein binders. Approximately 5% of total semm folate is being transported by high... 

Two classes of antioxidants are known the low-molecular weight compounds (tocopherols, ascorbate, -carotene, glutathione, uric acid and etc.) and the proteins (albumin, transferrin, caeruloplasmin, ferritin, etc.) including antioxidant enzymes (e.g. superoxide dismutase, catalase, glutathione peroxidase). 

Transferrin (from human or bovine serum) [11096-37-0] Mr 80,000. Purified by affinity... 

FIGURE 7.17 Separation of a complex mixture on Fractogel EMD BioSEC (S) with a column dimension of 1000 X 50 mm (Superformance glass column). The sample contained ferritin (I), immunoglobulin G (2), transferrin (3), ovalbumin (4), myoglobin (5), aprotinin (6), and vitamin B, (7). Five milliliters of the mixture was injected onto the column at a flow rate of 3 ml/min (eluent 20 mAI sodium phosphate buffer, 0.1 M NaCI, pH 7.2). 

A variety of cellular and viral proteins contain fatty acids covalently bound via ester linkages to the side chains of cysteine and sometimes to serine or threonine residues within a polypeptide chain (Figure 9.18). This type of fatty acyl chain linkage has a broader fatty acid specificity than A myristoylation. Myristate, palmitate, stearate, and oleate can all be esterified in this way, with the Cjg and Cjg chain lengths being most commonly found. Proteins anchored to membranes via fatty acyl thioesters include G-protein-coupled receptors, the surface glycoproteins of several viruses, and the transferrin receptor protein. 

Other non-haem proteins, distinct from the above iron-sulfur proteins are involved in the roles of iron transport and storage. Iron is absorbed as Fe" in the human duodenum and passes into the blood as the Fe protein, transferrin, The Fe is in a distorted octahedral environment consisting of 1 x N, 3x0 and a chelating carbonate ion which... 

CRP , complement , PLA2 , serum amyloid A , fibrinogen , c -acid glycoprotein , IL-1Ra , ceruloplasmin , ai-antichymotrypsin , LBP albumin , haptoglobin , IGF-1 , transferrin , u2-HS glycoprotein ... 

Transfer chemical potentials solvation metal ions, 2,298 Transferrins, 2, 772 6, 669... 

Aguas, A., Esaguy, N., Sunkel, C.E., Silva, M.T. (1990). Cross-reactivity and sequence homology between the 65 kilodalton mycobacterial heat shock protein and human lactoferrin, transferrin, and DR beta subsets of major histocompatibility complex class II molecules. Infect. Immun. 58, 1461-1470. 

F9 embryonal carcinoma cells have a simple set of growth supplements which are required for growth in serum-free medium insulin, transferrin, and fibronectin (Rizzino and Sato, 1978). Fibronectin is a component of the extracellular matrix and facilitates the attachment of the cells to the culture dish. In addition, high density lipoprotein (HDL) has been observed to promote the growth of F9 cells serum-free. 

Figure 10. Primary cultures of mouse kidney cells. Primary cultures of kidney epithelial cells derived from 10-day-old mice were grown either in hormonally defined medium with five supplements (5 pg/ml insulin, 5 pg/ml transferrin, 25 ng/ml PCE, 5 X10" M hydrocortisone, and 5 x 10" M Tj), or in medium supplemented with 10% fetal calf serum. After 10 days, primary cultures still were epithelial in morphology serum free (a) but were overgrown with fibroblasts with serum (b). (Taub et al., 1979 with permission.)...

Harris WR (1998) Binding and Transport of Nonferrous Metals by Serum Transferrin. 92 121-162... 

Strohmeier W (1968) Problem und Modell der homogenen Katalyse. 5 96-117 Sugiura Y, Nomoto K (1984) Phytosiderophores - Structures and Properties of Mugineic Acids and Their Metal Complexes. 58 107-135 Sun H, Cox MC, Li H, Sadler PJ (1997) Rationalisation of Binding to Transferrin Prediction of Metal-Protein Stability Constants. 88 71-102 Swann JC, see Bray RC (1972) II 107-144... 

Although iron deficiency is a common problem, about 10% of the population are genetically at risk of iron overload (hemochromatosis), and elemental iron can lead to nonen2ymic generation of free radicals. Absorption of iron is stricdy regulated. Inorganic iron is accumulated in intestinal mucosal cells bound to an intracellular protein, ferritin. Once the ferritin in the cell is saturated with iron, no more can enter. Iron can only leave the mucosal cell if there is transferrin in plasma to bind to. Once transferrin is saturated with iron, any that has accumulated in the mucosal cells will be lost when the cells are shed. As a result of this mucosal barrier, only about 10% of dietary iron is normally absorbed and only 1-5% from many plant foods. 

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