The CuI‐catalyzed azide–alkyne cycloaddition (CuAAC) has been established as a powerful coupling technology for the conjugation of proteins, nucleic acids, and polysaccharides. Nevertheless, several ...shortcomings related to the presence of Cu, mainly oxidative degradation by reactive oxygen species and sample contamination by Cu, have been pointed out. This Minireview discusses key aspects found in the development of the efficient and benign functionalization of biomacromolecules through CuAAC, as well as the Cu‐free strain‐promoted azide–alkyne cycloaddition (SPAAC).
Efficient and benign bioconjugation: CuI‐catalyzed azide–alkyne cycloaddition (CuAAC) is an established coupling method because of its high reliability and straightforward experimental procedure. However, the Cu catalyst has often proved detrimental to proteins, nucleic acids, and polysaccharides. CuI ligands and Cu‐free strain‐promoted procedures (SPAAC) have been developed that are efficient and avoid degradation of the resulting bioconjugates.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The generation of dendrimers is a powerful tool in the control of the size and biodistribution of polyion complexes (PIC). Using a combinatorial screening of six dendrimers (18–243 terminal groups) ...and five oppositely charged PEGylated copolymers, a dendrimer‐to‐PIC hierarchical transfer of structural information was revealed with PIC diameters that increased from 80 to 500 nm on decreasing the dendrimer generation. This rise in size, which was also accompanied by a micelle‐to‐vesicle transition, is interpreted according to a cone‐ to rod‐shaped progression in the architecture of the unit PIC (uPIC). This precise size tuning enabled dendritic PICs to act as nanorulers for controlled biodistribution. Overall, a domino‐like control of the size and biological properties of PIC that is not attainable with linear polymers is feasible through dendrimer generation.
PIC and choose: The size and biodistribution of polyion complexes (PICs) can be hierarchically tuned with the generation of a dendrimer component in a way not attainable with linear polymers.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The interaction of two anthocyanins with a water‐soluble polyanionic dendrimer was studied through UV/Vis, stopped‐flow, and NMR spectroscopy. Cyanidin‐3‐glucoside (cy3glc) revealed a stronger ...interaction than malvidin‐3‐glucoside (mv3glc) at pH 1 according to their apparent association constants. A higher color increased was also obtained for cy3glc at pH 3.5 as a result of this stronger interaction. A high‐frequency chemical shift of the cy3glc aromatic protons suggest the formation of ionic pairs. The interaction parameters (K≈700 m−1, n≈295) indicated the binding of approximately two anthocyanin molecules by each sulfate group. The equilibrium and rate constants of cy3glc in the presence of dendrimer showed an increased stability of the flavylium cation and a higher protection of this species from hydration (pK′a and pKh increased almost one pH unit). The tuning and color stabilization of anthocyanins by using this dendrimer allow novel applications as colorimetric sensors for food packaging.
True colors: The interaction of two anthocyanins, cyanidin‐3‐glucoside (cy3glc) and malvidin‐3‐glucoside (mv3glc), with a water‐soluble polyanionic dendrimer was studied through UV/Vis, stopped‐flow, and NMR spectroscopy. Cy3glc revealed a stronger interaction than mv3glc at pH 1 according to their apparent association constants. A higher color increased was also obtained for cy3glc at pH 3.5 as a result of this stronger interaction.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A polymer‐mediated paramagnetic spin relaxation (PSR) filter is presented for the selective suppression of signals from polymer‐interacting species in the 1D and 2D NMR spectra of mixtures. The ...combined use of Gd3+ and a polymer with a high transverse relaxation enhancement (R2p, which gives a measure of the Gd3+‐complexing ability) results in the suppression of signals from any polymer‐interacting component in mixtures, irrespective of their R2p. By using poly(acrylic acid) (PAA) as a model system, we demonstrate selective filtering of the signals of typical low‐R2p species (insensitive to Gd3+), such as molecular/polymeric cations and non‐ionic polymers, which, through PAA recognition (electrostatic/hydrogen‐bonding interactions), become exposed to the paramagnetic effect of Gd3+, while leaving non‐PAA‐interacting species unaffected. Typical suppression conditions involve PAA (approximately equimolar amount with respect to the species to be filtered) accompanied by sub‐mm concentrations of Gd3+ and T2‐filters ≤100 ms. Overall, by exploiting the PSR principles and the recognition properties of polymers, selective NMR filtrations that are not attainable by diffusion, relaxation, or direct PSR filters, can be achieved.
NMR spectral filtering: A polymer‐mediated paramagnetic spin relaxation filter has been devised for selective suppression of the signals of polymer‐interacting species in the 1D and 2D NMR spectra of mixtures (see graphic).
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
5.
Click Chemistry for Drug Delivery Nanosystems Lallana, Enrique; Sousa-Herves, Ana; Fernandez-Trillo, Francisco ...
Pharmaceutical research,
01/2012, Volume:
29, Issue:
1
Journal Article
Peer reviewed
Open access
ABSTRACT
The purpose of this Expert Review is to discuss the impact of click chemistry in nanosized drug delivery systems. Since the introduction of the click concept by Sharpless and coworkers in ...2001, numerous examples of click reactions have been reported for the preparation and functionalization of polymeric micelles and nanoparticles, liposomes and polymersomes, capsules, microspheres, metal and silica nanoparticles, carbon nanotubes and fullerenes, or bionanoparticles. Among these click processes, Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has attracted most attention based on its high orthogonality, reliability, and experimental simplicity for non-specialists. A renewed interest in the use of efficient classical transformations has been also observed (
e.g.
, thiol-ene coupling, Michael addition, Diels-Alder). Special emphasis is also devoted to critically discuss the click concept, as well as practical aspects of application of CuAAC to ensure efficient and harmless bioconjugation.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Multivalency is a key, ubiquitous phenomenon in nature characterized by a complex combination of binding mechanisms, with special relevance in carbohydrate–lectin recognition. Herein we introduce an ...original surface plasmon resonance kinetic approach to analyze multivalent interactions that has been validated with dendrimers as monodisperse multivalent analytes binding to lectin clusters. The method, based on the analysis of early association and late dissociation phases of the sensorgrams provides robust information of the glycoconjugate binding efficiency and real-time structural data of the binding events under the complex scenario of the glyco-cluster effect. Notably, it reveals the dynamic nature of the interaction and offers experimental evidence on the contribution of binding mechanisms.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Although growth factors and anti-apoptotic peptides have been shown to be neuroprotective in stroke models, translation of these experimental findings to clinic is hampered by limited penetration of ...peptides to the brain. Here, we show that a large peptide like the basic fibroblast growth factor (bFGF) and a small peptide inhibitor of caspase-3 (z-DEVD-FMK) can effectively be transported to the brain after systemic administration by incorporating these peptides to brain-targeted nanoparticles (NPs). Chitosan NPs were loaded with peptides and then functionalized by conjugating with antibodies directed against the transferrin receptor-1 on brain endothelia to induce receptor-mediated transcytosis across the blood—brain barrier (BBB). Pre-ischemic systemic administration of bFGF- or z-DEVD-FMK-loaded NPs significantly decreased the infarct volume after 2-hour middle cerebral artery occlusion and 22-hour reperfusion in mice. Co-administration of bFGF- or z-DEVD-FMK-loaded NPs reduced the infarct volume further and provided a 3-hour therapeutic window. bFGF-loaded NPs were histologically detected in the brain parenchyma and also restored ischemia-induced Akt dephosphorylation. The neuroprotection was not observed when receptor-mediated transcytosis was inhibited with imatinib or when bFGF-loaded NPs were not conjugated with the targeting antibody, which enables them to cross the BBB. Nanoparticles targeted to brain are promising drug carriers to transport large as well as small BBB-impermeable therapeutics for neuroprotection against stroke.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Click chemistry in combination with ultrafiltration has allowed the quick, efficient, and reliable multivalent conjugation of unprotected alkyne-derived carbohydrates to three generations of ...azido-terminated gallic acid−triethylene glycol dendrimers under aqueous conditions. The reported procedure allows the atom economical incorporation of up to 27 unprotected fucose, mannose, and lactose residues, in reproducible high yields (up to 92%), requiring only catalytic amounts of Cu. The completion of the conjugation process was clearly established in all cases by both 1H NMR and MALDI-TOF MS.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Experiments by Surface Plasmon Resonance (SPR) illustrate the relevance of lectin density for the reliable evaluation of binding efficiencies in surface-based multivalent carbohydrate recognition. ...The difference between affinity data obtained by solution and surface-based experiments is also stressed.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
PDF
