Multivalent architectures

The N-linked pentasaccharide core Man3(GlcNAc)2 glycopeptide bearing the extracellular MMP inducer sequence 517 (emmprin 34—58) has been successfully linked to G(l) PAMAM aminodendrimer by thioester activation (Fig. 63). The resulting octameric 30 kDa construct was obtained in low yield, but was purified by preparative electrophoresis and fully characterized by MALDI-TOF mass spectrometry. The multivalent architecture was built to evaluate the requirement of emmprin multimerization for inducing MMP expression.384... 

SCHEME 16.1 Structures of multivalent architectures and their general synthetic strategies, (a) Convergent approach, (b) Divergent approach. 

Fig. 3 Some archetypes of defined multivalent architectures compared to their natural counterparts...

Self-assembly via an induced stimulus was reported by Chilkoti etal. utilizing an elastin-like polypeptide that forms micelles at the critical micelle temperature (Figure 14). These induced multivalent architectures presenting RGD epitopes, designed to bind integrins, were shown to exhibit dynamic modulation of a receptorbinding affinity in response to an external trigger. ... 

Cationic liposomes form complexes with plasmid DNA. Also, in this case DOPE affects the architecture of the complexes. DOTAP liposomes without DOPE are able to condense DNA, while DOTAP/DOPE liposomes do not condense DNA, presumably due to Hn-phase formation [230,233]. Interestingly, multivalent cationic liposomes, such as DOGS, can condense DNA more efficiently than monovalent cationic liposomes [233]. If the complexation is carried out at high ionic strength the DNA condensation is less prominent than in plain water. 

Gestwicki JE, Cairo CW, Strong LE, Oetjen KA, Kiessling LL. Influencing receptor-ligand binding mechanisms with multivalent ligand architecture. J Am Chem Soc 2002 124 14922-14933. 

Fig. 5 Generation of multifunctionality/multivalency by self-assembly. Octa-valency from either hydrazide and dialdehyde components/subunits (left), or preformed ligands (top right) in the case of the formation of [2x2] grid-type metallosupramolecular architectures. Insert. Schematic representation of the generation of hexadeca-valency from tetrasubstituted ligand molecules...

These findings suggest that the mechanically threaded structure of polyrotaxanes with controlled number of threading a-CD molecules can have favorable thermodynamic effects on multivalent interactions. Finally, we have established the concept that the combination of multiple copies of ligands and their supramolecular mobility along the mechanically threaded polyrotaxane structure should contribute to the novel design of polymeric architectures aiming at enhanced multivalent interactions. 

While multivalency, self-assembly, and template effects provide strategies aiming at generating more and more complex architectures, supramolecular chemistry can also be utilized for controlling reactivity and even catalyzing reactions. Closely related to organocatalysis, supramolecular catalysts [39] accelerate reactions by... 

Architectures of Multivalent Glycomimetics for Probing Carbohydrate-Lectin Interactions... 

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