Biotin cell surface receptors

Biotin acts to induce glucokinase, phosphofructokinase, and pyruvate kinase (key enzymes of glycolysis), phosphoenolpyruvate carboxykinase (a key enzyme of gluconeogenesis), and holocarboxylase synthetase, acting via a cell-surface receptor linked to formation of cGMP and increased activity of RNA polymerase. The activity of holocarboxylase synthetase (Section 11.2.2) falls in experimental biotin deficiency and increases with a parallel increase in... 

Fig. 5 Schematic representation of the surface modification steps used by Ganger et al. to produce a biologically active surface in a microreactor. Biotin-labeled human anti- 5-integrin (HAI) was bound to modified PDMS and used to study cell surface receptor activity. (From Ref.. ) (View this art in color at www.dekker.com.)...

NHS esters of D-biotin have been used in many applications, including the biotinylation of rat IgE to study receptors on murine lymphocytes (Lee and Conrad, 1984), in the development of an immunochemical assay for a postsynaptic protein and its receptor (LaRochelle and Froehner, 1986a), in the study of plasma membrane domains by biotinylation of cell surface proteins in Dictyostelium disoideum amoebas (Ingalls et al., 1986), and for the detection of blotted proteins on nitrocellulose membranes after transfer from polyacrylamide electrophoresis gels (LaRochelle and Froehner, 1986b). 

The responses are typically initiated by the specific interaction of the environmentally encountered chemical with receptors that are deployed on the cell surface. Radiolabeled biotin, for example, interacts with a structurally selective receptor with an estimated affinity (as represented by the KD) of 400 pM this compares with a behavioral EC50 for this substance of 300 pM. Compounds that are structurally similar to biotin can compete for the binding of the radiolabeled molecule, whereas compounds that are structurally different cannot. 

In contrast to the high affinity biotin-(strept)avidin bonds, carbohydrate-L-selectin bonds with modest affinity stop white cells at vessel walls in the circulation. Numerous bonds to other surface (integrin) receptors then form between the white cell and vessel wall to sustain adhesion and enable subsequent movement into the surrounding tissue. On its initial arrest from the blood flow, the white cell can be subjected to forces of 100 pN in a time frame of milliseconds, which implies loading rates of lO -lO pN s . With this functional requirement in mind, we now examine recent tests of carbohydrate-L-selectin bonds under dynamic loading in probe tests. 

Fig. 10.9 pH-dependent biotin availability for binding, (a) Above pH 7.0, biotin anchored on the micelle core via pH-sensitive PHis is shielded by PEG shell of the micelle, (b) Biotin is exposed on the micelle surface at acidic conditions (6.5 < pH < 7.0) and can interact with cells, which facilitates biotin-receptor-mediated endocytosis. When the pH is further lowered (pH < 6.5), the micelle destabilizes, which enhances drug release, (modified and reproduced from [154], with permission from American Chemical Society)... 

To bring the nanocontainer to a specific place where it should release its pay-load, targeting is a required approach. Hence, much work has been carried out to attach ligands or antibodies to the hydroxyl end-group of PEG-based assemblies [150,181,243], Biotinylated nondegradable block copolymer assemblies have been shown to attach to surfaces coated with the biotin receptor avidin [146,147, 150,244], Coupling chemistry has been applied to conjugate either an antihuman IgG, or antihuman serum to PEG-carbonate- or PEG-polyester-assembled polymer vesicles [149,245], HIV-derived Tat peptide attached to PEG-PBD polymersomes enhanced the cellular delivery of nanoparticles [246] and increased dendritic cell uptake in vitro [181]. 

---