Peptides chimeric

Partidos C, Stanley C, Steward M. The influence of orientation and number of copies of T- cell and B-cell epitopes on the specificity and affinity of antibodies induced by chimeric peptides. Eur J Immunol 1992 22 2675. 

In this approach, chimeric peptides [79] are generated as transportable dmg derivatives targeting the receptor-mediated mechanism. Chimeric peptides are formed by hnking a dmg... 

Initial studies of brain delivery based on the chimeric peptide strategy used the absorptive-mediated uptake of cationized albumin which was chemically coupled to the opioid peptide P-endorphin [80] or its metabohcaUy stabilized analogue [D-Ala ]P-endorphin. Tracer experiments in which the chimeric peptide was labelled in the endorphin moiety provided evidence of internalization by isolated brain capillaries and transport into brain tissue in vivo [81]. 

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. 

The cargo that is suitable for transport by chimeric peptides encompasses a wide array of substances. Table 2.2 gives examples of studies, which measured CNS effects after peptide drug delivery. 

Table 2.2. Pharmacologic effects obtained with chimeric peptides in animal models.

Chimeric peptide Dose Mode of administration Animal model Effect... 

Figure 2.9. Differential pharmacological effect elicited by vector-mediated delivery of a VIP analogue. The organ blood flow in brain and salivary gland was measured in conscious rats after i.v. administration of vehicle (saline), the brain delivery vector OX26-SA, the VIP peptide alone, or the chimeric peptide. While cerebral blood flow increased in the chimeric peptide group by 60% compared to the saline control, the increase in salivary gland blood flow seen with the peptide alone was abolished by coupling to the vector. The VIP analogue was biotinylated with a non-cleavable 14-atom spacer (biotin-XX) for coupling to the vector. Data from reference [95].

Pardridge, W.M., D. Triguero, and J.L. Buciak. 1990. Beta-endorphin chimeric peptides Transport through the blood-brain barrier in vivo and cleavage of disulfide linkage by brain. Endocrinology 126 977. 

Greenfield, N. J., Montelione, G. T., Farid, R. S., and Hitchcock-DeGregori, S. E. (1998). The structure of the N-terminus of striated muscle a-tropomyosin in a chimeric peptide Nuclear magnetic resonance structure and circular dichroism studies. 

Design considerations in the development of effective chimeric peptides include vector specificity for the brain, vector pharmacokinetics, coupling between vector and drag, and intrinsic receptor affinity for the released drug. 

A 27 amino acid chimeric peptide with cell-penetrating properties. See Cell-Penetrating Peptides. See Pooga, M., Hallbrink, M., Zorko, M., and Lan-gel, ti.. Cell penetration by transportan, FASEB J. 12, 67-77,1998 Padiri, K., Saalik, P, Hansen, M. et al.. Cell transduction pathways of transpor-tans, Biooconjugate Chem. 16, 1399-1410, 2005. 

One purpose of this chapter is to highlight some key findings related to the properties and applications of chimeric peptides. No doubt the future will see a tangible change in the balance and distribution of green and red boxes in the subspace of all possible chimeric peptides. 

Case Study to Illustrate Multigeneric Character of Chimeric Peptides... 

We know nothing of the practical or conceptual limitations of chimeric peptide design and two potential caveats are apparent. 

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