Peptide dendrimers

E. A. B. Kantchev, C.-C. Chang, and D.-K. Chang, Direct Fmoc/tert-Bu solid phase synthesis of octamannosyl polylysine dendrimer-peptide conjugates, Biopolymers, 84 (2006) 232-240. 

Ghosh and coworkers demonstrate that discrete supramolecular assemblies can be formed from leucine-zipper peptides tethered to a dendrimer core. These give fibrous structures when two complementary discrete dendrimer-peptide assemblies are combined this is one of the first examples where both discrete and repeated assemblies can be formed using the same system (Figure 18a). 

Figure 18 Discrete and fibrous assemblies utilizing the dendrimer-peptide constructs of Ghosh et al. (a) Both discrete and extended systems can be formed from coiled-coil/dendrimer eonstructs TEM images of (b) protofibrils and (c) fibrils fonned from the self-assembling constructs. (Reproduced from Ref. 73. American Chemical Society, 2004.)...

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]. 

An interesting case in the perspective of artificial enzymes for enantioselective synthesis is the recently described peptide dendrimer aldolases [36]. These dendrimers utilize the enamine type I aldolase mechanism, which is found in natural aldolases [37] and antibodies [21].These aldolase dendrimers, for example, L2Dl,have multiple N-terminal proline residues as found in catalytic aldolase peptides [38], and display catalytic activity in aqueous medium under conditions where the small molecule catalysts are inactive (Figure 3.8). As most enzyme models, these dendrimers remain very far from natural enzymes in terms ofboth activity and selectivity, and at present should only be considered in the perspective of fundamental studies. 

Figure 3.8 Aldol reaction and peptide dendrimer catalyst.

Adler-Abramovich, L. Perry, R. Sagi, A. Gazit, E. Shabat, D. Controlled assembly of peptide nanotubes triggered by enzymatic activation of self-immolative dendrimers. Chem. Biochem. 2007, 8, 859-862. 

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. 

Two dendrimers based on Fe-porphyrin core carrying peptide-like branches of different sizes have been synthesized in order to have more open and a more densely packed (23) structures [43]. The electrochemical behavior has been examined in CH2C12 and in aqueous solution. In the less polar solvent, the two dendrimers show similar potentials for the Fem/Fen couple, suggesting that the iron porphyrins in both the more open and the more densely packed dendrimers experience similar microenvironments. On the contrary, in water the behavior of the two dendrimers is very different since the reduction from Fem to Fe11 is much easier for the densely packed dendrimer. This result can be explained considering that in the dendrimer with the relatively open structure the aqueous solvation of the iron porphyrin is still possible, whereas in the densely packed one the contact between the heme and the external solvent is signifi-... 

L. Crespo, G. Sanclimens, M. Pons, E. Giralt, M. Royo, and F. Albericio, Peptide and amide bond-containing dendrimers, Chem. Rev., 105 (2005) 1663-1681. 

Finally, dendrimers have been synthesized using solid phase peptide synthesis resins, wherein the core is linked to the resin and the half-dendrimer (dendron) is built out from it in sequential steps (Marsh et al., 1996 Swali et al., 1997 Wells et al., 1998). The advantage of this method... 

Monaghan, Sean, Griffith-Johnson, David, Matthews, Ian and Bradley, Mark (2001). Solid-phase synthesis of peptide-dendrimer conjugates for an investigation of integrin binding. Arkivoc, 2001, (Part (x)), 46-53. http //eprints.soton.ac.uk/19576/... 

When G2-OH is mixed with a fourfold molar excess of Cu + ions the spectrum in Fig. 9b results. These data indicate that each G2-OH can sorb at least four Cu + ions. Moreover, the separation between adjacent copper adducts is 62.5, which indicates that the oxidation state of Cu inside dendrimer during the MALDI-MS experiments is -1-1. Reflectron-mode MS also confirms this assignment the mass differences between the monoisotopic peaks of protonated dendrimers, singlecopper adducts, and double-copper adducts are 61.96 and 61.93, respectively, which is consistent with the assignment of the adduct ions as [Mis + Cu(l)]+ and [Mis + 2Cu(I)-H] +. We speculate that the presence of Cu+ is a consequence of the photochemical reduction of Cu + during ionization. Such photoreduction in MALDI MS measurements has been observed previously when polymers or peptides are used as ligands for Cu + [117,118]. 

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