Folic receptor

Wiener and co-workers used folic acid-conjugated Gd(DTPA)-PAMAM dendrimers for visualizing the high-affinity folate receptor, overexpressed in many tumors.201 The contrast agent accumulated in the cells, resulting in a remarkable contrast enhancement on 7)-weighted images. 

Immunosensors have been developed commercially mostly for medical purposes but would appear to have considerable potential for food analysis. The Pharmacia company has developed an optical biosensor, which is a fully automated continuous-flow system which exploits the phenomenon of surface plasmon resonance (SPR) to detect and measure biomolecular interactions. The technique has been validated for determination of folic acid and biotin in fortified foods (Indyk, 2000 Bostrom and Lindeberg, 2000), and more recently for vitamin Bi2. This type of technique has great potential for application to a wide range of food additives but its advance will be linked to the availability of specific antibodies or other receptors for the various additives. It should be possible to analyse a whole range of additives by multi-channel continuous flow systems with further miniaturisation. 

Thermal ablation using carbon nanotubes is a definite option for use in oncology, especially since nanotubes can be functionalized with targeting modalities like folic acid. Some cancer cell types express large numbers of folic acid receptors on... 

Fig. 10.14 Folic acid can be conjugated onto nanotubes fluorescently labeled nanotubes to target cells expressing folic acid receptors (a,b,c). Nanotubes conjugated with folic acid display a fluorescent signature indicating that nanotubes are internalized by cells expressing folic acid receptors (d). Without the folic acid conjugate, there is very little distribution of nanotubes within the cells as attributed by the lack of fluorescent signature in (e) (Reprinted from Kam et al., 2005. With permission from the National Academy of Sciences, USA) (See Color Plates)...

Receptor-mediated transporters are excipients that serve as substrates to exploit specific receptors present on cell membranes. Examples of various receptors that have been explored for permeation enhancement include bile acids (45), vitamin Bi2 (46), amino acids (47), and folic acid (48). Most of the work in receptor-mediated transporters is conducted via the use of prodrugs. For example, a prodrug of acyclovir conjugated to bile acids was seen to have higher permeability as compared to the original drug, because of receptor-mediated transport of the prodrug via bile acid transporters (49). 

Anderson KE, Eliot LA, Stevenson BR, Rogers JA. Formulation and evaluation of a folic acid receptor-targeted oral vancomycin liposomal dosage form. Pharm Res 2001 18(3) 316-322. 

Sulfa drugs have a close structural resemblance to PABA. When taken by a person suffering from a bacterial infection, a sulfa drug is transformed by the body to the compound sulfanilamide, which attaches to the bacterial receptor sites designed for PABA, as shown in Figure 14.7, thereby preventing the synthesis of folic acid. Without folic acid, the bacteria soon die. The patient, however, because he or she receives folic acid from the diet, lives on. 

Folate coenzymes, 803, 804. See also Folic acid Folate receptors 805 3-Fold axis 333 Folding patterns... 

As described in Box 11-C, the ameboid cells of the slime mold Dictyostelium discoideum are attracted to nutrients such as folic acid during their growth stage. Later, as the cells undergo developmental changes they become attracted by pulses of cyclic AMP.330 Occupancy of 7-helix receptors for cAMP on the outer plasma membrane appears to induce methylation of both proteins and phospholipids and a rise in cytosolic Ca2+ and changes in the cytoskeleton that result in preferential extension of the actin-rich pseudopods toward the chemoattractant.331... 

Receptor mediated endocytosis, on the other hand, requires recognition by the receptor before internalization of the molecule. So far, two receptor mediated endocytosis protocols have mainly been studied for potential applications in MRI contrast enhancement, namely the transferrin and folic acid receptor systems. 

Phosphonoformic acid (Foscarnet), an antiviral drug, which consists of carboxylic acid and phosphate linked together, was shown to be absorbed in the small intestine by the phosphate carrier-mediated mechanism [154], The transport of folic acid was investigated in biopsy specimens of intestinal mucosa from healthy volunteers. A pH-dependent, active transport of folic acid was found in the proximal small intestine, whereas in the mucosa of the colon, folic acid uptake was driven by a facilitated diffusion, mediated by a low-affinity carrier [155]. The existence of folate receptors in the human colonic mucosa is logical due to the large amounts of folic acid produced by the colonic flora [145],... 

Folic acid, shown in Fig. 12.3, is a common component of food and vitamins.36 The receptor for the vitamin folic acid is known as the folate receptor or the high-affinity membrane folate-binding protein.37 These folate receptors typically are not present in normal cells, but in a variety of human tumors they are greatly overexpressed.36-38 In addition, folate receptors mediate internalization by endocytosis. For these reasons, folic acid has been examined as a homing device. In general, studies have shown that by simple conjugation of folic acid to macromolecules, internalization into cells can occur similarly to that of free folic acid.39... 

Some of the structural properties which have been ascribed to DA receptors appear to deserve attention for their heuristic value, but painfully few should engender much confidence in their reality. A sobering lesson is available from analysis of complexes of dihydrofolate reductase (], 8). Methotrexate is a very close analog of folic acid and is a potent inhibitor of the enzyme, but it is now almost certain that these ligands bind in the enzyme active site in aspects differing by a rota-... 

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