Control of protein–ligand recognition using a stimuli-responsive polymer

Stayton, Patrick S.; Shimoboji, Tsuyoshi; Long, Cynthia J.; Chilkoti, Ashutosh; Chen, Guohua; Harris, J. Milton; Hoffman, Allan S.

doi:10.1038/378472a0

Cited by 666 publications

(462 citation statements)

References 27 publications

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“…1A). Although this dissociation constant is substantially higher than the dissociation constant for unbound biotin and streptavidin in solution, this result is consistent with reports of polymer conjugation and biotin-streptavidin affinity (17,18). To demonstrate streptavidin binding to the peptide nanofibers, we visualized the peptides with and without streptavidin using atomic force microscopy (AFM).…”

Section: Resultssupporting

confidence: 73%

Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

Davis

Hsieh²,

Takahashi³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

552

405

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Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a ''biotin sandwich'' approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to peptide nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin I in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy.engineering ͉ maturation ͉ scaffold

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Section: Resultssupporting

confidence: 73%

Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

Davis

Hsieh²,

Takahashi³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

552

405

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“…[15][16][17][18][19] However, N-OR gels, consisting of chemically crosslinked networks, used so far had several important limitations, such as low volume change and slow deswelling rate, as well as poor mechanical properties. Among these disadvantages, slow rates of deswelling have been studied most extensively.…”

Section: Stimuli Sensitivitiesmentioning

confidence: 99%

“…To date, extensive studies have been conducted into the feasibility of using PNIPA hydrogels in various systems such as artificial insulin-control systems, 15 efficient bioseparation devices, 16 drug delivery systems 17 and biotechnological and tissue engineering devices. 18,19 Among the various types of polymer hydrogels, 'chemically crosslinked polymer hydrogels' have been widely used in academic studies as well as for practical applications, such as soft contact lenses and superabsorbent polymers, because their network composition and degree of crosslinking can be easily controlled. PNIPA hydrogels described above have also been prepared by chemical crosslinking using an organic crosslinker.…”

Section: Nanocomposite Gels Disadvantages Of Polymer Hydrogelsmentioning

confidence: 99%

Synthesis and properties of soft nanocomposite materials with novel organic/inorganic network structures

Haraguchi

2011

Polym J

202

164

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We have fabricated new types of polymer hydrogels and polymer nanocomposites, that is, nanocomposite gels (NC gels) and soft polymer nanocomposites (M-NCs), with novel organic/inorganic network structures. Both NC gels and M-NCs were synthesized by in situ free-radical polymerization in the presence of exfoliated clay platelets in aqueous systems and were obtained in various forms and sizes with a wide range of clay contents. Here, disk-like inorganic clay nanoparticles function as multifunctional crosslinkers to form new types of network systems. NC gels have extraordinary optical, mechanical and swelling/deswelling properties, as well as a number of new characteristics relating to optical anisotropy, polymer/clay morphology, biocompatibility, stimuli-sensitive surfaces, micropatterning and so on. The M-NCs also exhibit dramatic improvements in optical and mechanical properties including ultrahigh reversible extensibility and well-defined yielding behavior, despite their high clay contents. Thus, the serious disadvantages (intractability, mechanical fragility, optical turbidity, poor processing ability, low stimulus sensitivity and so on) associated with the conventional, chemically crosslinked polymeric materials were overcome in NC gels and M-NCs. Keywords: clay; hydrogel; mechanical properties; nanocomposite; network INTRODUCTIONPolymer nanocomposites (P-NCs), composed of organic polymer and inorganic nanoparticles, have been widely investigated in the last three decades to develop new, value-added polymeric materials based on existing polymers. [1][2][3][4] To date, many P-NCs consisting of various polymers and inorganic nanoparticles (for example, silica, silsesquioxane, titania, clay, carbon nanotubes) have been developed by using sol-gel reactions of metal alkoxides or organic premodification of nanoparticles. [1][2][3][4][5] The resulting P-NCs show significant improvements in some properties, such as modulus, heat-distortion temperature, hardness, gas impermeability and so on. However, the P-NCs developed so far have encountered inherent difficulties in preparation and processing as the inorganic content increases. In the case of polymer/ clay nanocomposites, in general, only a few weight percent of clay can actually be incorporated into NCs (o10 wt%, at the most) in the form of organic modified clay. 2,4,5 Further increases in clay content often cause structural inhomogeneities because of inadequate dispersion or irregular aggregation of the clay, and always result in disadvantageous optical and mechanical properties and processability.To overcome these limitations, we extend the concept of 'organic/ inorganic nanocomposites' to the field of soft materials, such as 'polymer hydrogels' and 'soft polymers,' under the strategy of fabricating novel organic/inorganic structures. In the present article, we give an overview of the development of two types of soft nanocomposites,

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“…2 In one of their earliest examples, a genetically modified mutant of streptavidin, in which a cysteine residue was introduced near the outer edge of the biotin binding pocket, was conjugated with a vinyl sulfone terminated thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) chain. 8 Below the LCST of the PNIPAAm, the biotin binding properties of the polymer-protein conjugate were identical to those of the unmodified mutant or the wild-type streptavidin. At temperatures above the LCST of the PNIPAAm, however, an 84% decrease in the biotin binding capacity was observed, which was ascribed to the collapse of the PNIPAAm chain and the consequent blocking of the biotin binding site.…”

Section: Modulation Of Binding and Recognition Propertiesmentioning

confidence: 88%

“…At temperatures above the LCST of the PNIPAAm, however, an 84% decrease in the biotin binding capacity was observed, which was ascribed to the collapse of the PNIPAAm chain and the consequent blocking of the biotin binding site. 8 A more recent article described the conjugation of a different thermosensitive polymer, poly(N,N-diethylacrylamide) (PDEAAm), to streptavidin at a position slightly further away from the binding pocket. 57 In this case, the expansion of the PDEAAm chain below its LCST prevented the binding of biotinylated proteins.…”

Section: Modulation Of Binding and Recognition Propertiesmentioning

confidence: 99%

Biological–synthetic hybrid block copolymers: Combining the best from two worlds

Klok

2004

J. Polym. Sci. A Polym. Chem.

273

141

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ABSTRACT:Although biopolymers and synthetic polymers share many common features, each of these two classes of materials is also characterized by a distinct and very specific set of advantages and disadvantages. Combining biopolymer elements with synthetic polymers into a single macromolecular conjugate is an interesting strategy for synergetically merging the properties of the individual components and overcoming some of their limitations. This article focuses on a special class of biological-synthetic hybrids that are obtained by site-selective conjugation of a protein or peptide and a synthetic polymer. The first part of the article gives an overview of the different liquid-phase and solidphase techniques that have been developed for the synthesis of well-defined, that is, site-selectively conjugated, synthetic polymer-protein hybrids. In the second part, the properties and potential applications of these materials are discussed. The conjugation of biological and synthetic macromolecules allows the modulation of protein binding and recognition properties and is a powerful strategy for mediating the self-assembly of synthetic polymers. Synthetic polymer-protein hybrids are already used as medicines and show significant promise for bioanalytical applications and bioseparations.

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Control of protein–ligand recognition using a stimuli-responsive polymer

Cited by 666 publications

References 27 publications

Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction

Synthesis and properties of soft nanocomposite materials with novel organic/inorganic network structures

Biological–synthetic hybrid block copolymers: Combining the best from two worlds

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