Peptide approach

Development of a peptide vaccine is derived from the identification of the immunodominant epitope of an antigen (141). A polypeptide based on the amino acid sequence of the epitope can then be synthesized. Preparation of a peptide vaccine has the advantage of allowing for large-scale production of a vaccine at relatively low cost. It also allows for selecting the appropriate T- or B-ceU epitopes to be included in the vaccine, which may be advantageous in some cases. Several vaccines based on peptide approaches, such as SPf66 (95) for malaria and an HIV-1 peptide (142) have been in clinical trials. No peptide vaccines are Hcensed as yet. 

Preterm labour is the major cause of perinatal morbidity and mortality. Oxytocin antagonists offer an attractive approach to prevention. Chapter 7 reviews three decades of medicinal chemistry in this field. The peptide approach has resulted in valuable injectable products. Selectivity over the related vasopressin receptors and improvement in pharmacokinetic profile have been the key challenges for more recent non-peptide programmes, and these seem likely to yield orally available medicines. 

Studies on artificial ion channels are expected to provide important information on molecular mechanisms and to deepen our understanding of natural ion channels through the establishment of a detailed structure-function relationship. At the same time, the research will contribute to the fascinating area of nanoscale transducers, and may eventually lead to the development of so-called molecular ionics. Here, the author would like to describe the basic concept for the molecular design of various artificial ion channels and to compare their characteristics in the hope of stimulating a future explosion of this research field. Special attention is focused on non-peptidic approaches. Helical bundle approaches " and studies on modified antibiotics " are beyond the scope of this review. 

Structure-function studies of IFN-y carried out using the synthetic peptide approach and site-specific antibodies indicated that both the N- and C-terminal regions of the protein were not only functionally important, but also accessible at the surface of the molecule. The x-ray crystal structure of human IFN-y has been determined and reveals that in the IFN-y homodimer both the N- and the... 

Signature-peptide approach to detecting proteins in complex mixtures. 

A model complex was acmally synthesised, but in this model complex the peptide linker that would eventually carry the pharmaceutically relevant targeting group (TG) was replaced by an alkyl group. The validity of the peptide approach could not be proven. 

Characterization of epitope regions of thyrotropin b-subunit recognized by the monoclonal antibodies mAb279 and mAb299 a chimeric peptide approach. /. Pept. Res. 54, 218-229. 

L. Riggs, C. Sioma, F. Regnier, Automated signature peptide approach for proteomics, J. Chromatogr. A, 924 (2001) 359. 

Figure 5.10 SeLf-assembLing tubes of cyclic peptides and their effect on cell membranes (a) cyclooctapeptide showing central cavity (b) cyclic peptides approach a phospholipid membrane (c) insertion initiated (d) tube formation (e) membrane disruption...

Ringe, D. Burley, S. K. Petsko, G. A. In Synthetic Peptides Approaches to Biological Problems Alan R. Liss New York 1989 p. 87. 

The cyclic peptide approach to nanotubes has some advautages over all other methods. In addition to diameter control, one can highlight that the properties of the outer surface of the nanotube can easily be modified by varying the amino acid side chains. In addition, due to the Cn symmetry of the backbone skeleton, nonsymmet-rical CPs can form an infinite number of different SPN (Figure 23b). This phenomenon is based on the interstrand rotation between two consecutive CPs, to form nonequivalent interactions for each j8-sheet. Appropriate unit design and optimization of conditions for self-assembly allows the nanotube properties to be tailored for specific applications. As a result, SPN can be used as (or in) porous solid materials, soluble cylindrical supermolecules, ion channels and other transmembrane pores, soUd-supported ion sensors, antimicrobial and cytotoxic agents, and nanocluster composites. A recent review published by Granja et al. includes the most relevant examples in this area. ... 

Gauthier, J. Bruderlein, F. Aubry, N. Rakhit, S. Valois, S. Bousquet, Y. In Synthetic Peptides Approaches to Biological Problems. Tam, J.P., and Kaiser, E.T. Eds. UCLA Symposia on Molecular and Cellular Biology,... 

Figure 41.9 Miller s peptide approach to the acylative KR of racemic alcohols.

Hernandez, J.-F., Olivera, B. M., Cruz, L. J., Myers, R. A., Abbott, J. and Rivier, J. 1990. Synthesis, characterization and biological activity of conantokin-G analogs. In UCLA Symposia Conference on Biochemical and Biomedical Engineering Synthetic Peptides Approaches to Biological Problems Frisco, CO, February 22-March 4,... 

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