1421676-62-1Relevant articles and documents
Synthesis and functionalization of dendritic polyglycerol-based nanogels: application in T cell activation
álvaro-Benito, Miguel,Dernedde, Jens,Dimde, Mathias,Freund, Christian,Haag, Rainer,Reisbeck, Felix,Schmitt, Ann-Cathrin,Wedepohl, Stefanie
, p. 96 - 106 (2022/01/03)
The concept of multivalency finds various applications in the fields of chemistry and biology, relying on the principle that multiple weak interactions can lead to strong adhesive forces. Polymeric carriers are promising tools to translate these properties into the field of biomedicine, especially upon functionalization by active biomolecules, such as antibodies. In this study we report on the synthesis of dendritic polyglycerol (dPG) and dPG-based nanogels (NGs) as platforms for the multivalent display of molecules and their potential application as carrier units. Macromolecules based on dPG were synthesized and NGs were generated by strain-promoted azide-alkyne cycloaddition (SPAAC) by inverse nanoprecipitation under mild conditions. Scale-up screening rendered a reproducible method for a batch size of up to 50 mg for the formation of NGs in a size range of 150 nm with narrow dispersity. Dye-labelled bovine serum albumin (FITC-BSA) was chosen as a model protein and showed successful conjugation to the carriers, while the protein's secondary structure was not affected. Consequently, cyanine-5-amine (Cy5-NH2) and avidin (Av) were conjugated in order to exploit the strong avidin-biotin interaction, facilitating the directed attachment of a myriad of biotinylated (bio)molecules. As a proof-of-concept, the biotinylated monoclonal antibodies (mAbs) α-CD3 and α-CD28 were attached to the platforms and their capability to activate T cells was assessed. Experiments were performed with a Jurkat reporter cell line which expresses green fluorescent protein (GFP) upon activation, providing a rapid and reliable readout by flow cytometry. Carriers clearly outperformed conventional compounds for activation (i.e.antibodies crosslinked with anti-IgG antibody) at significantly lower dosages. These findings could be confirmed by confocal laser scanning microscopy (CLSM), showing accumulation of the functional nanoplatforms at the cell surface and cytoplasmic GFP expression (>95% activation of cells for the multivalent conjugates at 10 μg mL?1compared to 37% activation with conventionally crosslinked mAbs at 25 μg mL?1), whereas carriers without mAbs could not activate cells. As the attachment of biotinylated molecules to the functional nanoplatforms is straightforward, the results obtained show the great potential of our platforms for a broad range of applications.
ANTIBODY COMPOUNDS WITH REACTIVE ARGININE AND RELATED ANTIBODY DRUG CONJUGATES
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, (2020/05/19)
The present invention provides antibody compounds that contain a substitution of arginine for the reactive lysine residue (Lys99) in the hydrophobic cleft (38C2_Arg). The invention also provides antibody drug conjugate compounds (ADCs) that contain cargo
Gold Nanoparticles Functionalized with RGD-Semipeptides: A Simple yet Highly Effective Targeting System for αVβ3 Integrins
Maggi, Vito,Bianchini, Francesca,Portioli, Elisabetta,Peppicelli, Silvia,Lulli, Matteo,Bani, Daniele,Sole, Roberta Del,Zanardi, Franca,Sartori, Andrea,Fiammengo, Roberto
, p. 12093 - 12100 (2018/08/01)
Effective and selective targeting of the αVβ3 integrin subtype is of high relevance in cancer research for the development of therapeutic systems with improved efficacy and of diagnostic imaging probes. We report here a new class of highly selective, αVβ3-targeted gold nanoparticles (AuNPs), which carry cyclic 4-aminoproline-RGD semipeptides (cAmpRGD) as the targeting moiety immobilized at low surface density on the poly(ethylene glycol) (PEG)-based nanoparticle coating. We show that these nanoparticles are potent inhibitors of the integrin-mediated melanoma tumor cell adhesion to vitronectin and are selectively internalized via receptor-mediated endocytosis. Furthermore, we have developed bifunctional cAmpRGD-functionalized AuNPs by conjugation of a fluorophore (FAM or TAMRA) to a separate set of reactive groups on the PEG-based coating. These bifunctional AuNPs not only recapitulate the binding properties of cAmpRGD-AuNPs but also can be visualized via confocal laser microscopy, allowing direct observation of nanoparticle internalization. The peculiar molecular design of these nanoparticles and their precisely defined architecture at the molecular level accounts for their selective integrin binding with very low nonspecific background.
NOVEL CONJUGATES, PREPARATION THEREOF, AND THERAPEUTIC USE THEREOF
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, (2012/09/11)
Provided herein are cryptophycin conjugates and compositions containing them. Methods of making and using such compounds also are provided
"clickable", polymerized liposomes as a versatile and stable platform for rapid optimization of their peripheral compositions
Kumar, Amit,Erasquin, Uriel J.,Qin, Guoting,Li, King,Cai, Chengzhi
supporting information; experimental part, p. 5746 - 5748 (2010/09/15)
A versatile and stable liposomal platform is developed for rapid optimization of its peripheral composition. The platform is based on polydiacetylene lipids terminated with alkynyl groups. Conditions for copper-catalyzed azide-alkyne cycloaddition (a "click" reaction) are optimized for rapid attachment of azides with controlled composition onto the liposomes.
