(2007) Synthesis and characterization of immobilized PAMAM dendrons.
The acetylation was performed first to obtained more uniform distribution of the functional groups within nanodevice (ND) molecules and decrease their toxicity since positively charged (amino terminated) PAMAM dendrimers are know to be toxic (). Biotin (BT) was selected as reporter moiety for ND detection using labeled antibodies. In addition it is much smaller compared to commonly used fluorescent dyes that can potentially affect biological activity of NDs. Lastly carboxyl groups of succinamic acid were used for cRGD peptides conjugation via amid bound with lysine side chain amino group, which is not involved in binding of the peptide to αvβ3 integrins. Derivatives in each synthetic step were purified and characterized by polyacrylamide gel electrophoresis (PAGE), size exclusion chromatography equipped with three detectors: multiangle laser light scattering, UV-vis diode-array and refractive index (SEC-MALLS-DAD-RI), potentiometric acid-base titration, matrix assisted laser desorption ionization - time of flight (MALDI-TOF) mass spectrometry and nuclear magnetic resonance (NMR), providing complementary results for thorough analysis.
synthesis and characterization ..
In 2007, Banaszak Holl etal. employed SPR to measure the increasedavidity to FBP and cellular uptake of G5 PAMAM–FA conjugatesas a function of average number of attached FAs (Figure ). The dissociation constant(kd) was observed to exponentially decreaseas the average valency of FA increased; however, this calculationassumed that given a long enough experiment all bound materials woulddissociate from the surface and that the experimental sensorgram wouldreturn to the level of signal present prior to G5–FAn(avg) exposure. The nonlinear (exponential) behaviorin kd was attributed to a saturation ofFA–FBP binding events limited by the immobilized protein densityon the SPR flow cell surface and not to the valency of FA (Figure a). Interestingly, the same trend in signal saturationas a function of FA valency was observed for mean fluorescence, asmeasured by flow cytometry when equivalent conjugates labeled witha dye were evaluated for binding to FAR upregulated KB cells. Thisobservation was interpreted as an indication that the dendrimer conjugatesdo not trigger receptor clustering on the cell surface, which wouldallow for higher affinities as more proteins became available.
Multivalent conjugation of folicacid has been employed to targetcells overexpressing folate receptors. Such polymer conjugates havebeen previously demonstrated to have high avidity to folate bindingprotein. However, the lack of a monovalent folic acid–polymermaterial has prevented a full binding analysis of these conjugates,as multivalent binding mechanisms and polymer-mass mechanisms areconvoluted in samples with broad distributions of folic acid-to-dendrimerratios. In this work, the synthesis of a monovalent folic acid–dendrimerconjugate allowed the elucidation of the mechanism for increased bindingbetween the folic acid–polymer conjugate and a folate bindingprotein surface. The increased avidity is due to a folate-keyed interactionbetween the dendrimer and protein surfaces that fits into the generalframework of slow-onset, tight-binding mechanisms of ligand/proteininteractions.
Objective To synthesis and characterization nano-composite ..
Preparation, Characterization, and Application of Poly(vinyl alcohol)-graft-Poly(ethylene glycol) Resins: Novel Polymer Matrices for Solid-Phase Synthesis.
synthesis and characterization of dendrimer …
We are developing a novel Systemic Targeted Radiation Therapy (START) approach utilizing a dendrimer-based platform to detect and treat primary and metastatic cancers. As a first step using poly(amidoamine) (PAMAM) dendrimer we have synthesized the multifunctional nanodevice that selectively binds to αvβ3 integrins. PAMAM dendrimers are water soluble, well-defined polymers, built from symmetric dendrons, containing β-alanine subunits, emanating from a core (,). These polymers are nearly ideal delivery vehicles as they are not broken down by enzymes and are generally removed from the bloodstream by the filter organs (–). PAMAMs can be prepared to be non-immunogenic, non-mutagenic and non-toxic (see e.g. ). Modifiable terminal functionalities of dendrimers offer a multipurpose mode to covalently attach drugs, diagnostic/imaging modules and targeting moieties (). PAMAMs have been already used as delivery vehicles for oligonucleotides, antisense oligonucleotides, oligonucleotide arrays and chemotherapeutic cancer drugs (–). They have also been utilized as templates for composite nanoparticles, which allows them to host inorganic nanoclusters () thus providing a way to integrate desirable properties of inorganic materials and biofriendly polymers, and yielding several new imaging and therapy applications (–).
Synthesis and characterization of low-generation ..
Combination of Ring-Opening Polymerization and "Click" Chemistry for the Synthesis of an Amphiphilic Tadpole-Shaped Poly(ε-Caprolactone) Grafted by PEO.