Peptide optimal peptides

The specificity determinants surrounding the tyrosine phospho-acceptor sites have been determined by various procedures. In PTK assays using various substrates, it was determined that glutamic residues of the N-terminal or C-terminal side of the acceptor are often preferred. The substrate specificity of PTK catalytic domains has been analyzed by peptide library screening for prediction of the optimal peptide substrates. Finally, bioinformatics has been applied to identify phospho-acceptor sites in proteins of PTKs by application of a neural network algorithm. 

BOX 4.3. EVOLUTION OF SOMATOSTATIN PEPTIDE—OPTIMIZED FOR PHARMACEUTICAL PROPERTIES... 

Fig. (4). The primary structures of enod40 peptides. Enod40 peptides are compared from legumes with determinate nodules (a), legumes with indeterminate nodules (b), and non-legumes (c). Gaps (-) were introduce to optimize the alignment. The invariant residues are shown in bold face. The figure was modified after [79],...

The use of peptide libraries to study T cell specificity was first demonstrated by Gundlach et al.45 Since then studies have focused on T cell specificity with emphasis on the identification of immunodominant epitopes in infectious diseases and autoimmune disorders, and on the determination of tumor antigens. The PS-SCL approach, as described above, was successfully used to study T cell recognition and to identify and optimize peptides having a range of activities in stimulating proliferative responses, cytokine production, and/or lysis by CD4+ and CD8+ murine and human T cell clones and T cell lines of known and unknown specificity.46-53... 

In optimizing peptide orprtein delivery, buccal administration is sometimes... 

Structures of the Ala-X peptides optimized by ab initio methods show clear trends toward lower values of the dihedral angle < > as the X side chain becomes larger while structures optimized using semiempirical and empirical force fields do not show trends. 

Traditionally, the specificity of proteases is determined using standard or optimized peptide libraries containing small recognition sites or, for de novo screening, phage display libraries (Richardson, 2002). These techniques may prove to be useful as a first screening approach. However, they are insufficient to predict the outcome of inhibiting a proteolytic activity in an in vivo situation. 

Given the limitations of the above systems, it is apparent that the optimal peptide model of a p-sheet (and a p-turn) should be as analagous to the monomeric helix models as possible. In particular, the ideal p-sheet model should be small (< 20 residues), monomeric, water-soluble, pure (composed of only p-sheets and p-turns), amphipathic (to investigate sidedness), reversibly denaturable, composed of only natural amino acids, easily synthesized and easily characterized by standard spectroscopic techniques. We believe that we have developed such a peptide model. It is based on the naturally occurring cyclic peptide gramicidin S, an antibiotic produced by the bacterium bacillus brevis (12). The schematic structure of gramicidin S as determined by X-ray and NMR studies (13, 14) is shown in Figure 1. 

In optimizing peptide or protein delivery, buccal administration is sometimes preferred. The buccal membrane is a stratified squamous epithelium, and the intercellular spaces are filled by cellular extrusion products. 

Peptide catalysts, peptides that catalyze chemical reactions such as aldol, retro-aldol, and Michael reactions. In contrast to enzymes or catalytic antibodies ( abzymes), small peptides often display limited catalytic activity and substrate specificity. Combinatorial methods combined with reaction-based or catalysis-based high-throughput selection approaches are suited for catalyst optimization [E. Tanaka, Chem. Record 2005, 5, 276]. 

Approximately 2—3 leads Resynthesized on resin Chromatographic format Actual feed stream Optimized elution conditions Optimized peptide density... 

The excellent resolving power of RPC has made it the predominant HPLC technique for peptide separations, and its ability to separate peptides of closely related struetures makes it extremely useful for high-speed, analytical and preparative applications. Not only is RPC usually superior to other modes of HPLC with respeet to both speed and efficiency, but it also offers the widest scope for manipulation of mobile phase conditions to optimize peptide separations. 

Scheme 5.10 Optimized peptide ligands for a Pd-catalyzed allylic addition and a desymmetrization reaction.

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