Peptide-based complexes

Complex peptide mixmres can now be analyzed without prior purification by tandem mass spectrometry, which employs the equivalent of two mass spectrometers linked in series. The first spectrometer separates individual peptides based upon their differences in mass. By adjusting the field strength of the first magnet, a single peptide can be directed into the second mass spectrometer, where fragments are generated and their masses determined. As the sensitivity and versatility of mass spectrometry continue to increase, it is displacing Edman sequencers for the direct analysis of protein primary strucmre. 

Robertsone aZ. defined these elaborate peptide-based inorganic model complexes using a term extracted from art and architecture, maquette,... 

Snapper and Hoveyda reported a catalytic enantioselective Strecker reaction of aldimines using peptide-based chiral titanium complex [Eq. (13.11)]. Rapid and combinatorial tuning of the catalyst structure is possible in their approach. Based on kinetic studies, bifunctional transition state model 24 was proposed, in which titanium acts as a Lewis acid to activate an imine and an amide carbonyl oxygen acts as a Bronsted base to deprotonate HCN. Related catalyst is also effective in an enantioselective epoxide opening by cyanide "... 

In the field of biopolymer chromatography, monolithic columns, based on copolymerization of silane precursors, have predominately been investigated regarding separation of peptides and complex protein digests, whereas their application to analysis of high-molecules-weight analytes like proteins or dsDNA fragments is scarcely reported. 

The cysteinyl proteases include papain calpains I and II cathepsins , H, and L proline endopeptidase and interleukin-converting enzyme (ICE) and its homologs. The most well-studied cysteinyl protease is likely papain, and the first x-ray crystallographic structures of papain [193] and a peptide chloromethylketone inhibitor-papain complex [194] provided the first high resolution molecular maps of the active site. Pioneering studies in the discovery of papain substrate peptide-based inhibitors having P, electrophilic moieties such as aldehydes [195], ketones (e.g., fluoromethylketone, which has been determined [196] to exhibit selectivity for cysteinyl proteases versus serinyl proteases), semicarbazones, and nitriles are noteworthy since 13C-NMR spectro-... 

The same group extended their work recently to the synthesis of a peptide-based device detecting Zn2+ in aqueous solutions. [441 The principle is to add a dansyl fluorophore on a Lys side chain of a synthetic Zn finger peptide. Upon complexation of Zn2+, an important conformational change occurs that brings the fluorophore into a different environment and leads to a change in the fluorescence properties. 

The development of chiral peptide-based metal catalysts has also been studied. The group of Gilbertson has synthesized several phosphine-modified amino adds and incorporated two of them into short peptide sequences.[45J,71 They demonstrated the formation of several metal complexes, in particular Rh complexes, and reported their structure as well as their ability to catalyze enantioselectively certain hydrogenation reactions.[481 While the enantioselectivities observed are modest so far, optimization through combinatorial synthesis will probably lead to useful catalysts. The synthesis of the sulfide protected form of both Fmoc- and Boc-dicyclohexylphosphinoserine 49 and -diphenylphosphinoserine 50 has been reported, in addition to diphenylphosphino-L-proline 51 (Scheme 14).[49 To show their compatibility with solid-phase peptide synthesis, they were incorporated into hydrophobic peptides, such as dodecapeptide 53, using the standard Fmoc protocol (Scheme 15).[451 For better results, the phosphine-modified amino acid 50 was coupled as a Fmoc-protected dipeptide 56, rather than the usual Fmoc derivative 52.[471 As an illustrative example, the synthesis of diphe-nylphosphinoserine 52 is depicted in Scheme 16J45 ... 

Anti-deoxyribonucleic acid autoantibodies from human and mice suffering from Lupus erythematosus can penetrate into cells and accumulate in the cell nucleus. Based on the characteristics of a mi-ON A autoantibodies, VAYISRGGVSTYYSDTVKGRFTRQKYNKRA peptide (P3), which exhibits a-helix, has been used as a vector for the intracytoplasmic and intranuclear translocation of macromolecules (Table 16.7) (Avrameas et al., 1998, 1999). P3 shares similar capabilities with Antenapedia peptide (Derossi et al., 1994), but in contrast P3 operates only at 37 °C by an energy dependent mechanism. P3 linked to a 19 lysine residue sequence (K19-P3) forms complexes with plasmid DNA. Efficient transfection of mouse 3T3 cells and hamster lung CCL39 cells were obtained with these complexes. This transfection was not impaired by the presence of serum and did not require helper molecules such as chloroquine. These observations suggest that peptides from cell specific anti-DNA autoantibodies may represent a source of peptide-based gene delivery system with different specificities. 

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