Protein dendrimer

A COMMERCIAL EXAMPLE OF DENDRIMER-PROTEIN CONJUGATE-BASED REAGENT TECHNOLOGY... 

Recently three murine antisera to PAMAM dendrimers have been generated using dendrimer-protein conjugates as immunogens [9, 10]. The recognition properties of the three sera are exquisitely specific, recognizing unmodified... 

PAMAM dendrimers or modified PAMAM dendrimers (with oxiamine or sulfhydryl surface functionalities) exclusive of one another. These antisera recognize den-drimers in ELISA (enzyme-linked immunosorbent assays), dot blots and Western blots. The immunogenicity of dendrimer-protein conjugates has implications for therapeutic use of dendrimers as vaccines and we anticipate that antidendrimer antibodies will have applications in patterning and assembling nanostructures containing dendrimers. 

Western blots of dendrimer-protein conjugates can also be used to characterize the valency of protein-dendrimer conjugates. 

E. Gabellieri, G. B. Strambini, D. Shcharbin, B. Klajnert and M. Bryszewska, Dendrimer-protein interactions studied by tryptophan room temperature phosphorescence. Biochimica et Biophys-icaActa, 1764,1750-1756 (2006). 

The field of synthetic enzyme models encompasses attempts to prepare enzymelike functional macromolecules by chemical synthesis [30]. One particularly relevant approach to such enzyme mimics concerns dendrimers, which are treelike synthetic macromolecules with a globular shape similar to a folded protein, and useful in a range of applications including catalysis [31]. Peptide dendrimers, which, like proteins, are composed of amino acids, are particularly well suited as mimics for proteins and enzymes [32]. These dendrimers can be prepared using combinatorial chemistry methods on solid support [33], similar to those used in the context of catalyst and ligand discovery programs in chemistry [34]. Peptide dendrimers used multivalency effects at the dendrimer surface to trigger cooperativity between amino acids, as has been observed in various esterase enzyme models [35]. 

Figure 28 A dendrimer-based approach for the design of globular protein mimic using glutamic (Glu) and aspartic (Asp) acids as the building blocks and adamantyl as the core [151].

Anionic poly(amidoamine) (PAMAM) dendrimer was selected as a model of the soluble acidic-rich proteins to prepare CaC03 film on a poly(ethylenimine) film [49]. The CaCOj/polylethylenimine) composite film was obtained in the... 

Qualmann and Kessels have reported the synthesis of carborane-containing lysine dendrimers (123) (Fig. 72), with a better defined number of boron atoms, for use as protein labels in immunocytochemistry using electron microscopic techniques such as electron energy loss spectroscopy (EELS) and electron spectroscopic imaging (ESI).149... 

Other types of branched peptide dendrimers, known as multiple antigen peptides (MAPs), have been synthesized to mimic proteins for applications, for instance as synthetic vaccines, serodiagnostics, peptide inhibitors and intracellular delivery vehicles. Since this concept has been recently described in detail elsewhere [11], only the conceptual framework will be briefly presented here. Tam and coworkers have developed a dendritic core based on lysine units for the construction of MAPs [12-15] (Fig. 3). Carrying antigens at their periphery these MAPs have been designed to increase antigenicity and immunogenicity of peptides. 

In a more recent paper, Roy et al. reported on the synthesis and biological pro -perties of mannosylated Starburst dendrimers [46]. In addition to the presence of good biological properties in ligand- and inhibitor-tests, these dendrimers were shown to constitute novel biochromatography materials of high affinity for the rapid and easy isolation and purification of carbohydratebinding proteins from crude mixtures. 

Porphyrin complexes are particularly suitable cores to construct dendrimers and to investigate how the behavior of an electroactive species is modified when surrounded by dendritic branches. In particular, dendritic porphyrins can be regarded as models for electron-transfer proteins like cytochrome c [42, 43]. Electrochemical investigation on Zn-porphyrins bearing polyether-amide branches has shown that the first reduction and oxidation processes are affected by the electron-rich microenvironment created by the dendritic branches [42]. Furthermore, for the third generation compound all the observed processes become irreversible. 

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