scholarly journals NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

2015 ◽  
Vol 11 ◽  
pp. 50-60 ◽  
Author(s):  
Boris Schmidtgall ◽  
Claudia Höbartner ◽  
Christian Ducho
Keyword(s):  
Stereoselective Synthesis ◽  
Solid Phase ◽  
Building Blocks ◽  
Automated Synthesis ◽  
Site Specific ◽  
Dna Oligonucleotides ◽  
Modified Dna ◽  
Significant Step ◽  
Bioactive Agents ◽  
Oligonucleotide Analogues

Modifications of the nucleic acid backbone are essential for the development of oligonucleotide-derived bioactive agents. The NAA-modification represents a novel artificial internucleotide linkage which enables the site-specific introduction of positive charges into the otherwise polyanionic backbone of DNA oligonucleotides. Following initial studies with the introduction of the NAA-linkage at T–T sites, it is now envisioned to prepare NAA-modified oligonucleotides bearing the modification at X–T motifs (X = A, C, G). We have therefore developed the efficient and stereoselective synthesis of NAA-linked 'dimeric' A–T phosphoramidite building blocks for automated DNA synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues.

scholarly journals Modular automated solid phase synthesis of dermatan sulfate oligosaccharides

2014 ◽  
Vol 50 (15) ◽  
pp. 1875-1877 ◽  
Author(s):  
Jeyakumar Kandasamy ◽  
Frank Schuhmacher ◽  
Heung Sik Hahm ◽  
James C. Klein ◽  
Peter H. Seeberger
Keyword(s):  
Solid Phase Synthesis ◽  
Dermatan Sulfate ◽  
Solid Phase ◽  
Building Blocks ◽  
Automated Synthesis ◽  
Phase Synthesis ◽  
Iduronic Acid

Orthogonally protected d-galactosamine and l-iduronic acid building blocks and a photo-cleavable linker are instrumental for the automated synthesis of dermatan sulfate oligosaccharides.

Automated glycopeptide assembly by combined solid-phase peptide and oligosaccharide synthesis

2014 ◽  
Vol 50 (15) ◽  
pp. 1851-1853 ◽  
Author(s):  
Mattan Hurevich ◽  
Peter H. Seeberger
Keyword(s):  
Amino Acid ◽  
Solid Phase ◽  
Building Blocks ◽  
Solid Support ◽  
Automated Synthesis ◽  
Oligosaccharide Synthesis ◽  
Polystyrene Beads ◽  
Single Instrument

Automated synthesis of glycopeptides was achieved using monosaccharide and amino acid building blocks. Using polystyrene beads equipped with photo-labile linker as solid support, all synthetic manipulations were performed using a single instrument.

scholarly journals DNA functionalization by dynamic chemistry

2016 ◽  
Vol 12 ◽  
pp. 2136-2144 ◽  
Author(s):  
Zeynep Kanlidere ◽  
Oleg Jochim ◽  
Marta Cal ◽  
Ulf Diederichsen
Keyword(s):  
Deoxyribonucleic Acid ◽  
Solid Phase ◽  
Building Blocks ◽  
Thermodynamic Control ◽  
Dna Templates ◽  
Phase Synthesis ◽  
Dynamic Combinatorial Chemistry ◽  
Dna Oligonucleotides ◽  
Reversible Reactions ◽  
Modified Nucleobases

Dynamic combinatorial chemistry (DCC) is an attractive method to efficiently generate libraries of molecules from simpler building blocks by reversible reactions under thermodynamic control. Here we focus on the chemical modification of DNA oligonucleotides with acyclic diol linkers and demonstrate their potential for the deoxyribonucleic acid functionalization and generation of libraries of reversibly interconverting building blocks. The syntheses of phosphoramidite building blocks derived from D-threoninol are presented in two variants with protected amino or thiol groups. The threoninol building blocks were successfully incorporated via automated solid-phase synthesis into 13mer oligonucleotides. The amino group containing phosphoramidite was used together with complementary single-strand DNA templates that influenced the Watson–Crick base-pairing equilibrium in the mixture with a set of aldehyde modified nucleobases. A significant fraction of all possible base-pair mismatches was obtained, whereas, the highest selectivity (over 80%) was found for the guanine aldehyde templated by the complementary cytosine containing DNA. The elevated occurrence of mismatches can be explained by increased backbone plasticity derived from the linear threoninol building block as a cyclic deoxyribose analogue.

Selective Functionalization at N2-Position of Guanine in Oligonucleotides via Reductive Amination

2020 ◽  
Author(s):  
Bapurao Bhoge ◽  
Ishu Saraogi
Keyword(s):  
Organic Chemistry ◽  
Chemical Biology ◽  
Reductive Amination ◽  
The Other ◽  
Dna Oligomers ◽  
Site Specific ◽  
Wide Applicability ◽  
Dna Oligonucleotides ◽  
Selective Functionalization

Chemo- and site-specific modifications in oligonucleotides have wide applicability as mechanistic probes in chemical biology. Here we have employed a classical reaction in organic chemistry, reductive amination, to selectively functionalize the N<sup>2</sup>-amine of guanine/2’-deoxyguanine monophosphate. This method specifically modifies guanine in several tested DNA oligonucleotides, while leaving the other bases unaffected. Using this approach, we have successfully incorporated desired handles chemoselectively into DNA oligomers.

Development of Strategies for Glycopeptide Synthesis: An Overview on the Glycosidic Linkage

2020 ◽  
Vol 24 (21) ◽  
pp. 2475-2497
Author(s):  
Andrea Verónica Rodríguez-Mayor ◽  
German Jesid Peralta-Camacho ◽  
Karen Johanna Cárdenas-Martínez ◽  
Javier Eduardo García-Castañeda
Keyword(s):  
Chemical Synthesis ◽  
Solid Phase ◽  
Building Blocks ◽  
Heterogeneous Environments ◽  
Phase Synthesis ◽  
Low Concentrations ◽  
Biological Sources ◽  
Synthetic Routes ◽  
The Impact ◽  
Potential Use

Glycoproteins and glycopeptides are an interesting focus of research, because of their potential use as therapeutic agents, since they are related to carbohydrate-carbohydrate, carbohydrate-protein, and carbohydrate-lipid interactions, which are commonly involved in biological processes. It has been established that natural glycoconjugates could be an important source of templates for the design and development of molecules with therapeutic applications. However, isolating large quantities of glycoconjugates from biological sources with the required purity is extremely complex, because these molecules are found in heterogeneous environments and in very low concentrations. As an alternative to solving this problem, the chemical synthesis of glycoconjugates has been developed. In this context, several methods for the synthesis of glycopeptides in solution and/or solid-phase have been reported. In most of these methods, glycosylated amino acid derivatives are used as building blocks for both solution and solid-phase synthesis. The synthetic viability of glycoconjugates is a critical parameter for allowing their use as drugs to mitigate the impact of microbial resistance and/or cancer. However, the chemical synthesis of glycoconjugates is a challenge, because these molecules possess multiple reaction sites and have a very specific stereochemistry. Therefore, it is necessary to design and implement synthetic routes, which may involve various protection schemes but can be stereoselective, environmentally friendly, and high-yielding. This review focuses on glycopeptide synthesis by recapitulating the progress made over the last 15 years.

Fully Automated Parallel Oligonucleotide Synthesizer

2001 ◽  
Vol 66 (8) ◽  
pp. 1299-1314 ◽  
Author(s):  
Michal Lebl ◽  
Christine Burger ◽  
Brett Ellman ◽  
David Heiner ◽  
Georges Ibrahim ◽  
...  
Keyword(s):  
Solid Phase ◽  
Building Blocks ◽  
Solid Support ◽  
Continuous Operation ◽  
Gear Pump ◽  
Oligonucleotide Synthesis ◽  
Center Of Rotation ◽  
Microtiter Plates ◽  
The Individual ◽  
Design And Construction

Design and construction of automated synthesizers using the tilted plate centrifugation technology is described. Wash solutions and reagents common to all synthesized species are delivered automatically through a 96-channel distributor connected to a gear pump through two four-port selector valves. Building blocks and other specific reagents are delivered automatically through banks of solenoid valves, positioned over the individual wells of the microtiterplate. These instruments have the following capabilities: Parallel solid-phase oligonucleotide synthesis in the wells of polypropylene microtiter plates, which are slightly tilted down towards the center of rotation, thus generating a pocket in each well, in which the solid support is collected during centrifugation, while the liquid is expelled from the wells. Eight microtiterplates are processed simultaneously, providing thus a synthesizer with a capacity of 768 parallel syntheses. The instruments are capable of unattended continuous operation, providing thus a capacity of over two millions 20-mer oligonucleotides in a year.

scholarly journals Synthesis and Self-assembly of Amphiphilic Precision Glycomacromolecules

2021 ◽  
Author(s):  
Alexander Banger ◽  
Julian Sindram ◽  
Marius Otten ◽  
Jessica Kania ◽  
Alexander Strzelczyk ◽  
...  
Keyword(s):  
Self Assembly ◽  
Solid Phase ◽  
Building Blocks ◽  
Polymer Synthesis

We present the synthesis of so called amphiphilic glycomacromolecules (APGs) by using solid-phase polymer synthesis. Based on tailor made building blocks, monosdisperse APGs with varying compositions are synthesized, introducing carbohydrate...

scholarly journals Dual, Site-Specific Modification of Antibodies by Using Solid-Phase Immobilized Microbial Transglutaminase

ChemBioChem ◽  
2017 ◽  
Vol 18 (19) ◽  
pp. 1923-1927 ◽  
Author(s):  
Philipp R. Spycher ◽  
Christian A. Amann ◽  
Jöri E. Wehrmüller ◽  
David R. Hurwitz ◽  
Olivier Kreis ◽  
...  
Keyword(s):  
Solid Phase ◽  
Microbial Transglutaminase ◽  
Site Specific ◽  
Specific Modification ◽  
Dual Site
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