Peptide transferrin

Key Words Peptide nucleic acid delivery cell-penetrating peptides transferrin antisense. 

Fig. 2. Possible ways to deliver a PNA oligomer over cell- and nuclear membrane by peptides. Transferrin receptor mediated uptake (2) is endocytotic CPP-mediated uptake (1) goes via a seemingly energy-independent route. The efficiency of some steps (shown in dashed line) is not completely proven and may be very low under certain experimental conditions.

A synthetic peptide has been designed to mimic the effects of viral fusogenic properties (114,115). It consists of 30 amino acids with the major repeat of Glu-Ala-Leu-Ala so, it is referred to as a GALA peptide. It undergoes a conversion from an aperiodic conformation at neutral pH and becomes an amphipathic alpha helix at pH 5. In the more acidic environment, the peptide interacts with lipid bilayers (114,115). GALA has been incorporated into transferrin-targeted liposome, with the effect of significantly... 

Wagner E, Plank C, Zatloukal K, et al. Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes toward a synthetic virus-like gene-transfer vehicle. Proc Natl Acad Sci USA 1992 89(17) 7934-7938. 

Simoes S, Slepushkin V, Gaspar R, et al. Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides. J Biol Chem 1998 5(7) 955-964. 

Kakudo T, Chaki S, Futaki S, et al. Transferrin-modified liposomes equipped with a pH-sensitive fusogenic peptide an artificial viral-like delivery system. Biochemistry 2004 43(19) 5618-5628. 

Epidermal growth factor (EGF), low-density lipoprotein (LDL), and transferrin (Tfn) are often used as model peptides because all three are taken up via clathrin-mediated endocytosis, but they are sorted into different pathways after endocytosis. 

Simoes S, Slepushkin V, Pretzer E, et al. Transfection of human macrophages by lipoplexes via the combined use of transferrin and pH-sensitive peptides. J Leukoc Biol 1999 65(2) 270-279. 

Figure 2.8. Scheme of a chimeric peptide with examples for each of the distinct domains. 0X26, anti-rat transferrin receptor monoclonal antibody (mAh) 84-15, anti-human insulin receptor mAh cHSA, cationized human serum albumin VIP, vasoactive intestinal polypeptide DALDA, dermorphin analogue NGF, nerve growth factor BDNF, brain-derived neurotrophic factor PNA, peptide nucleic acid (3-gal, (3-galactosidase. 

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. 

Similar to the approaches followed with cyanine dyes (Chapter 3.1.3), attempts to enhance the selectivity of photosensitizers by conjugating to target-specific vehicles have been described [98]. The approaches included conjugates with antibodies [99, 100], antibody fragments [58, 101], peptides [102], the serum proteins albumin and transferrin [103,104] and estradiol [105]. 

Some proteins are imported into cells from the surrounding medium examples in eukaryotes include low-density lipoprotein (LDL), the iron-carrying protein transferrin, peptide hormones, and circulating proteins destined for degradation. The proteins bind to receptors in invaginations of the membrane called coated pits, which concentrate endocytic receptors in preference to other cell-surface proteins. The pits are coated on their cytosolic side with a lattice of the protein clathrin, which forms closed polyhedral structures (Fig. 27-40). The clathrin lattice grows as more recep-... 

A biological example of E° is the reduction of Fe(III) in the protein transferrin, which was introduced in Figure 7-4. This protein has two Fe(III)-binding sites, one in each half of the molecule designated C and N for the carboxyl and amino terminals of the peptide chain. Transferrin carries Fe(III) through the blood to cells that require iron. Membranes of these cells have a receptor that binds Fe(III)-transferrin and takes it into a compartment called an endosome into which H is pumped to lower the pH to —5.8. Iron is released from transferrin in the endosome and continues into the cell as Fe(II) attached to an intracellular metal-transport protein. The entire cycle of transferrin uptake, metal removal, and transferrin release back to the bloodstream takes 1-2 min. The time required for Fe(III) to dissociate from transferrin at pH 5.8 is —6 min, which is too long to account for release in the endosome. The reduction potential of Fe(IH)-transferrin at pH 5.8 is E° = —0.52 V, which is too low for physiologic reductants to reach. 

Transferrins. Within the body iron is moved from one location to another while bound as Fe3+ to transferrins, a family of related 680- to 700-residue 80-kDa proteins.38 49-53 Each transferrin molecule contains two Fe+3 binding sites, one located in each of two similar domains of the folded peptide chain. A dianion, usually CO 2, is bound together with each Fe3+. 

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