Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chemoselective ligation in the functionalization of polysaccharide-based particles.

ABSTRACT: Despite the promise of precisely targeted or otherwise functionalized polymeric particulate drug delivery vehicles, typical biocompatible particles are generally not amenable to facile and selective surface modification. Herein, we report the development of a simple, mild, and chemoselective strategy for the conjugation of biologically active molecules to the surface of dextran-based microparticles. Alkoxyamine-bearing reagents were used to form stable oxime conjugates with latent aldehyde functionality present in reducing carbohydrate chain ends. We demonstrate the functionalization of dextran-based microparticles with a fluorophore as well as a cell-penetrating peptide sequence, which facilitated the delivery of cargo to nonphagocytic cells leading to a 60-fold increase in the expression of a reporter gene when plasmid DNA-loaded particles were used.

SUBMITTER: Beaudette TT

PROVIDER: S-EPMC2759380 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Chemoselective ligation in the functionalization of polysaccharide-based particles.

Beaudette Tristan T TT Cohen Joel A JA Bachelder Eric M EM Broaders Kyle E KE Cohen Jessica L JL Engleman Edgar G EG Fréchet Jean M J JM

Journal of the American Chemical Society 20090801 30

Despite the promise of precisely targeted or otherwise functionalized polymeric particulate drug delivery vehicles, typical biocompatible particles are generally not amenable to facile and selective surface modification. Herein, we report the development of a simple, mild, and chemoselective strategy for the conjugation of biologically active molecules to the surface of dextran-based microparticles. Alkoxyamine-bearing reagents were used to form stable oxime conjugates with latent aldehyde funct ...[more]

PMID: 19591467

Similar Datasets

Chemoselective cross-linking and functionalization of alginate via Staudinger ligation.

Project description:In this study, we demonstrate the applicability of functionalized alginate to serve as a platform for the covalent cross-linking or immobilization of complementary phosphine functionalized groups via the chemoselective Staudinger ligation scheme. Azide groups were covalently linked to alginate through a heterobifunctional polyethylene glycol (PEG) linker and carbodiimide. Degree of azide functionalization was varied as a function of carbodiimide concentration and determined by proton nuclear magnetic resonance ((1)H NMR) and infrared spectroscopy. Spontaneous and covalently cross-linked alginate-PEG gels were generated via the Staudinger ligation scheme upon incubation of the azide functionalized alginate with PEG chains having 1-methyl-2-diphenylphosphino-terephthalate (MDT) as end groups. Modulation of the MDT to N(3) ratio resulted in variability of gel characteristics. In addition, azide functionalized alginate retained its capacity to instantaneously form hydrogels via electrostatic interaction with multivalent cations such as Ca(2+) and Ba(2+). Subsequently, covalent linkage of phosphine functionalized agents postgelation of the alginate was feasible, as illustrated via linkage of MDT-PEG-carboxyfluorescein. Capitalization of the chemoselective and cell compatible Staudinger ligation scheme for covalent cross-linking of alginate hydrogels may enhance the utility of this polymer for the stable encapsulation of various cell types, in addition to their use in the immobilization of labeling agents, proteins, and other bioactive molecules.

| S-EPMC2996242 | biostudies-literature

Glycoconjugate synthesis using chemoselective ligation.

Project description:Chemoselective ligation of carbohydrates and polypeptides was achieved using an adipic acid dihydrazide cross-linker. The reducing end of a carbohydrate is efficiently attached to peptides in two steps, constructing a glycoconjugate in high yield and with high regioselectivity, enabling the production of homogeneous glycoconjugates.

| S-EPMC6431789 | biostudies-literature

Liposome surface functionalization based on different anchoring lipids via Staudinger ligation.

Project description:Liposome surface functionalization facilitates numerous potential applications of liposomes, such as enhanced stability, bioactive liposome conjugates, and targeted drug, gene and image agent delivery. Anchoring lipids are needed for grafting ligands of interest and play important roles in ligand grafting density, liposome stability, and liposome chemical and physical characteristics as well. In this report, glyco-functionalized liposome systems based on two kinds of anchoring lipids, phosphatidylethanolamine (PE) and cholesterol (Chol), were prepared by post chemically selective functionalization via Staudinger ligation. The size and stability of the liposomes were confirmed by dynamic light scattering (DLS). Particularly, the impact of anchor lipids on the stability of glyco-functionalized liposomes was investigated by comparing two different anchor lipids, namely Chol-PEG2000-TP and DSPE-PEG2000-TP. In addition, the encapsulation and releasing capacity of the glycosylated liposome based on the two anchoring lipids were investigated by entrapping 5,6-carboxyfluorescein (CF) dye and monitoring the fluorescence leakage, respectively. Furthermore, the density and accessibility of grafted carbohydrate residues on the liposome surface were evaluated for the two anchoring lipid-derived liposomes with lectin binding, respectively.

| S-EPMC3955738 | biostudies-literature

Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation.

Project description:The recent synthesis of pyrimidine ribonucleoside-2',3'-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of ribonucleic acid (RNA) at an early stage in the origin of life. However, a prebiotic conversion of these weakly activated monomers, and their purine counterparts, to the 3',5'-linked RNA polymers of extant biochemistry has been lacking (previous attempts led only to short oligomers with mixed linkages). Here we show that the 2'-hydroxyl group of oligoribonucleotide-3'-phosphates can be chemoselectively acetylated in water under prebiotically credible conditions, which allows rapid and efficient template-directed ligation. The 2'-O-acetyl group at the ligation junction of the product RNA strand can be removed under conditions that leave the internucleotide bonds intact. Remarkably, acetylation of mixed oligomers that possess either 2'- or 3'-terminal phosphates is selective for the 2'-hydroxyl group of the latter. This newly discovered chemistry thus suggests a prebiotic route from ribonucleoside-2',3'-cyclic phosphates to predominantly 3',5'-linked RNA via partially 2'-O-acetylated RNA.

| S-EPMC4074891 | biostudies-literature

Vinylphosphonites for Staudinger-induced chemoselective peptide cyclization and functionalization.

Project description:In this paper, we introduce vinylphosphonites for chemoselective Staudinger-phosphonite reactions (SPhR) with azides to form vinylphosphonamidates for the subsequent modification of cysteine residues in peptides and proteins. An electron-rich alkene is turned into an electron-deficient vinylphosphonamidate, thereby inducing electrophilic reactivity for a following thiol addition. We show that by varying the phosphonamidate ester substituent we can fine-tune the reactivity of the thiol addition and even control the functional properties of the final conjugate. Furthermore, we observed a drastic increase in thiol addition efficiency when the SPhR is carried out in the presence of a thiol substrate in a one-pot reaction. Hence, we utilize vinylphosphonites for the chemoselective intramolecular cyclization of peptides carrying an azide-containing amino acid and a cysteine in high yields. Our concept was demonstrated for the stapling of a cell-permeable peptidic inhibitor for protein-protein interaction (PPI) between BCL9 and beta-catenin, which is known to create a transcription factor complex playing a role in embryonic development and cancer origin, and for macrocyclization of cell-penetrating peptides (CPPs) to enhance the cellular uptake of proteins.

| S-EPMC6598645 | biostudies-literature

Chemoselective ligation of sulfinic acids with aryl-nitroso compounds.

Project description:Making a comeback: The inefficient condensation of sulfinic acid and aryl nitroso compounds has been transformed into a chemoselective process that converts sulfinic acid into stable cyclic sulfonamide analogues (see scheme). This ligation proceeds rapidly under aqueous conditions in high yield, and lays the groundwork for the development of sulfinic acid detection methods in biological systems.

| S-EPMC3523331 | biostudies-literature

General chemoselective and redox-responsive ligation and release strategy.

Project description:We report a switchable redox click and cleave reaction strategy for conjugating and releasing a range of molecules on demand. This chemoselective redox-responsive ligation (CRRL) and release strategy is based on a redox switchable oxime linkage that is controlled by mild chemical or electrochemical redox signals and can be performed at physiological conditions without the use of a catalyst. Both conjugation and release reactions are kinetically well behaved and quantitative. The CRRL strategy is synthetically modular and easily monitored and characterized by routine analytical techniques. We demonstrate how the CRRL strategy can be used for the dynamic generation of cyclic peptides and the ligation of two different peptides that are stable but can be selectively cleaved upon changes in the redox environment. We also demonstrate a new redox based delivery of cargoes to live cells strategy via the CRRL methodology by synthesizing a FRET redox-responsive probe that is selectively activated within a cellular environment. We believe the ease of the CRRL strategy should find wide use in a range of applications in biology, tissue engineering, nanoscience, synthetic chemistry, and material science and will expand the suite of current conjugation and release strategies.

| S-EPMC3983135 | biostudies-literature

Chemoselective Installation of Amine Bonds on Proteins through Aza-Michael Ligation.

Project description:Chemical modification of proteins is essential for a variety of important diagnostic and therapeutic applications. Many strategies developed to date lack chemo- and regioselectivity as well as result in non-native linkages that may suffer from instability in vivo and adversely affect the protein's structure and function. We describe here the reaction of N-nucleophiles with the amino acid dehydroalanine (Dha) in a protein context. When Dha is chemically installed in proteins, the addition of a wide-range N-nucleophiles enables the rapid formation of amine linkages (secondary and tertiary) in a chemoselective manner under mild, biocompatible conditions. These new linkages are stable at a wide range of pH values (pH 2.8 to 12.8), under reducing conditions (biological thiols such as glutathione) and in human plasma. This method is demonstrated for three proteins and is shown to be fully compatible with disulfide bridges, as evidenced by the selective modification of recombinant albumin that displays 17 structurally relevant disulfides. The practicability and utility of our approach is further demonstrated by the construction of a chemically modified C2A domain of Synaptotagmin-I protein that retains its ability to preferentially bind to apoptotic cells at a level comparable to the native protein. Importantly, the method was useful for building a homogeneous antibody-drug conjugate with a precise drug-to-antibody ratio of 2. The kinase inhibitor crizotinib was directly conjugated to Dha through its piperidine motif, and its antibody-mediated intracellular delivery results in 10-fold improvement of its cancer cell-killing efficacy. The simplicity and exquisite site-selectivity of the aza-Michael ligation described herein allows the construction of stable secondary and tertiary amine-linked protein conjugates without affecting the structure and function of biologically relevant proteins.

| S-EPMC5799870 | biostudies-literature

Unified Approach to the Chemoselective α-Functionalization of Amides with Heteroatom Nucleophiles.

Project description:Functionalization at the α-position of carbonyl compounds has classically relied on enolate chemistry. As a result, the generation of a new C-X bond, where X is more electronegative than carbon requires an oxidation event. Herein we show that, by rendering the α-position of amides electrophilic through a mild and chemoselective umpolung transformation, a broad range of widely available oxygen, nitrogen, sulfur, and halogen nucleophiles can be used to generate α-functionalized amides. More than 60 examples are presented to establish the generality of this process, and calculations of the mechanistic aspects underline a fragmentation pathway that accounts for the broadness of this methodology.

| S-EPMC6879173 | biostudies-literature

Chemoselective modifications for the traceless ligation of thioamide-containing peptides and proteins.

Project description:Thioamides are single-atom substitutions of canonical amide bonds, and have been proven to be versatile and minimally perturbing probes in protein folding studies. Previously, our group showed that thioamides can be incorporated into proteins by native chemical ligation (NCL) with Cys as a ligation handle. In this study, we report the expansion of this strategy into non-Cys ligation sites, utilizing radical initiated desulfurization to "erase" the side chain thiol after ligation. The reaction exhibited high chemoselectivity against thioamides, which can be further enhanced with thioacetamide as a sacrificial scavenger. As a proof-of-concept example, we demonstrated the incorporation of a thioamide probe into a 56 amino acid protein, the B1 domain of Protein G (GB1). Finally, we showed that the method can be extended to ?-thiol amino acid analogs and selenocysteine.

| S-EPMC4927387 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data