Protein and peptide transport

For a series of 11 model peptides in an in vitro intestinal cell monolayer system, a good 

The diffusion of proteins and peptides in solution is dictated by the same considerations as those discussed in section 3.6. The rate of translational movement depends on the size of the molecule, its shape and interactions with solvent molecules. The rate of translational movement is often expressed by a frictional coefficient, f, defined in relation to the diffusion coefficient D, by equation (11.4)  

The diffusion coefficients and translational movements of proteins are important in considering the release of proteins from hydrogel matrix devices and other delivery vehicles, and in membrane transport, as far as this can be considered to be a passive diffusion process. Changes in shape during membrane transport in a lipid environment may also have to be considered. Table 11.6 gives some values of diffusion coefficient of a number of therapeutic peptides and proteins. 

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Adamski, RP Anderson, JL, Configurational Effects on Polystyrene Rejection from Micro-porosou Membranes, Journal of Polymer Science Part B Polymer Physics 25, 765, 1987. Adler, PM, Porous Media, Geometry and Transports Butterworth-Heinemann Boston, 1992. Afeyan, NB Fulton, SP Regnier, FE, Perfusion Chromatography Packing Materials for Proteins and Peptides, Journal of Chromatography 544, 267, 1991. 

YS Kim. Intestinal mucosal hydrolysis of proteins and peptides in peptide transport, and hydrolysis. A Ciba Foundation Symposium. Exerpta Medica. Amsterdam ... 

The amide functionality plays an important role in the physical and chemical properties of proteins and peptides, especially in their ability to be involved in the photoinduced electron transfer process. Polyamides and proteins are known to take part in the biological electron transport mechanism for oxidation-reduction and photosynthesis processes. Therefore studies of the photochemistry of proteins or peptides are very important. Irradiation (at 254 nm) of the simplest dipeptide, glycylglycine, in aqueous solution affords carbon dioxide, ammonia and acetamide in relatively high yields and quantum yield (0.44)202 (equation 147). The reaction mechanism is thought to involve an electron transfer process. The isolation of intermediates such as IV-hydroxymethylacetamide and 7V-glycylglycyl-methyl acetamide confirmed the electron-transfer initiated free radical processes203 (equation 148). 

Wang Z, Zhang Q (2004) Transport of proteins and peptides across human cultured alveolar A549 cell monolayer. Int J Pharm 269(2) 451—456... 

Bur M, Huwer H, Lehr CM, Hagen N, Guldbrandt M, Kim KJ, Ehrhardt C (2006) Assessment of transport rates of proteins and peptides across primary human alveolar epithelial cell monolayers. Eur J Pharm Sci 28(3) 196-203... 

Pulmonary administration of PNAs has great potential for the same reasons that pulmonary protein and peptide delivery have been successful. Predominantly, the distance for transport and ease of administration of agents are the advantages of pulmonary delivery, but the formulation of labile molecules for eventual pulmonary administration as lipid-based aerosols may be problematic. 

Hydrophilic polymers are currently undergoing investigation for improving the transport of biomacromolecules across the intestinal walls. Hydrophilic polymers have been shown to protect proteins and peptides from proteolysis. Multiple methods utilize the properties of polymers to protect biomacromolecules without removing them from the aqueous environment of the intestines. 

Charged solutes in electrolyte solutions that are electrokinetically driven through channels with nanoscale widths exhibit unique transport characteristics that may enable rapid and efficient separations under a variety of physiological and environmental conditions. Many biomolecules, including DNA, proteins, and peptides, are charged or can be complexed with charged surfactant molecules. Manipulating the velocity of biomolecules by variation in flow pressure or electric fields in channels of nanoscopic widths will enable efficient separations that are not possible in micro- or macroscopic channels. 

General tendencies in the in-vivo elimination of proteins and peptides may often be predicted from their physiological function. Peptides, for example, frequently have hormone activity and usually have short elimination half-lives. This is desirable for a close regulation of their endogenous levels and thus function. In contrast, transport proteins such as albumin or a-1 acid glycoprotein have elimination half-lives of several days or weeks, which enables and ensures the continuous maintenance of necessary concentrations in the bloodstream. 

The third mechanism is peritubular extraction of peptides and proteins from postglomerular capillaries and intracellular metabolism. Experiments using iodi-nated growth hormone (125I-rGH) have demonstrated that, while reabsorption into endocytic vesicles at the proximal tubule is still the dominant route of disposition, a small percentage of the hormone may be extracted from the peritubular capillaries [79, 86]. Peritubular transport of proteins and peptides from the baso-lateral membrane has also been shown for insulin [87] and the mycotoxin ochra-toxin A [88]. 

In this chapter we will mainly focus on questions related to the S-donor ligands. So, how can platinum reach the DNA after administration of the drug, after or despite its reactions with rescue agents, its transport through the cell membrane, and its possible binding to proteins and peptides as an intermediate ... 

Proteins and peptides have diverse functions in the cell. They form the structural components of muscle, connective tissue, hair, and nails. They catalyze reactions and transport ions and molecules across cell membranes. Met-enkephalin, for example, a peptide with four amide bonds found predominately in nerve tissue cells, relieves pain and acts as an opiate by producing morphine-like effects. 

Safe and effective delivery of peptides has also been successfully demonstrated in human studies using iontophoresis, a technique that uses mild electric current to facilitate transport of molecules across the skin. ° Iontophoresis works primarily by a combination of two forces, electro-repulsion of charged drug molecule away from the electrode and into the skin, and electroosmosis, a convective solvent flow in the direction of the counter-ion transport. In general, cationic proteins and peptides are delivered more efficiently than anionic molecules because electro-osmosis works in the same direction as electro-migration for cationic species. 

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