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.

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 The Breaking Beads Approach for Photocleavage from Solid Support

2020 ◽  
Author(s):  
yasmeen bakhatan ◽  
Israel Alshanski ◽  
Dana Grunhaus ◽  
Mattan Hurevich
Keyword(s):  
Continuous Flow ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
High Energy ◽  
Solid Support ◽  
Phase Synthesis ◽  
Polystyrene Beads ◽  
Magnetic Stirring ◽  
Photolabile Linkers

Photocleavage from polystyrene beads is a pivotal reaction for solid phase synthesis that relies on photolabile linkers. The photocleavage, usually performed by batch irradiation, suffers from incomplete and slow cleavage. To overcome these issues, continuous flow and high-energy lamps are frequently used, but these setups are hazardous, technically challenging, and expensive. We developed a photocleavage approach that relies on a benchtop LED lamp and magnetic stirring. In this approach, we crush the beads instead of keeping their integrity to increase the yield of photocleavage. This approach proved very efficient for photocleavage of protected oligosaccharides.

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.

scholarly journals Synthesis of glycosylated β3-homo-threonine conjugates for mucin-like glycopeptide antigen analogues

2010 ◽  
Vol 6 ◽  
Author(s):  
Florian Karch ◽  
Anja Hoffmann-Röder
Keyword(s):  
Amino Acid ◽  
Cancer Vaccines ◽  
Solid Phase ◽  
Building Blocks ◽  
Repeat Sequence ◽  
Amino Acid Derivative ◽  
Tandem Repeat Sequence ◽  
Important Target ◽  
Anti Cancer ◽  
Model Structures

Glycopeptides from the mucin family decorated with tumour-associated carbohydrate antigens (TACA) have proven to be important target structures for the development of molecularly defined anti-cancer vaccines. The strategic incorporation of β-amino acid building blocks into such mucin-type sequences offers the potential to create pseudo-glycopeptide antigens with improved bioavailability for tumour immunotherapy. Towards this end, TN and TF antigen conjugates O-glycosidically linked to Fmoc-β3-homo-threonine were prepared in good yield via Arndt–Eistert homologation of the corresponding glycosyl α-amino acid derivative. By incorporation of TN-Fmoc-β3hThr conjugate into the 20 amino acid tandem repeat sequence of MUC1 using sequential solid-phase glycopeptide synthesis, a first example of a mixed α/β-hybrid glycopeptide building block was obtained. The latter is of interest for the development of novel glycoconjugate mimics and model structures for anti-cancer vaccines with increased biological half-life.

3-(Tributylstannyl)allyl Alcohols: Useful Building Blocks for Solid-Phase Synthesis of Skipped Dienes and Trienes

2000 ◽  
Vol 65 (3) ◽  
pp. 434-454 ◽  
Author(s):  
Miroslav Havránek ◽  
Dalimil Dvořák
Keyword(s):  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Building Blocks ◽  
Solid Support ◽  
Stille Coupling ◽  
Phase Synthesis ◽  
Negative Results ◽  
Allyl Alcohols

Repeated Stille coupling of 3-substituted 3-(tributylstannyl)allyl alcohols 2 on a solid support was used to synthesize a 21 × 21 library of skipped dienes and a 21 × 21 × 21 library of skipped trienes. Starting 3-(tributylstannyl)allyl alcohols were prepared by Pd-catalyzed hydrostannation of substituted prop-2-yn-1-ols, by hydroalumination by LiAlH4 followed with transmetallation to tin using tributyltin methoxide, or by substitution of chlorine in (Z)-6-chloro-3-(tributylstannyl)hex-2-en-1-ol with appropriate nucleophile. Synthesized libraries were tested for the activity to endorphin receptors, but with negative results.

Principles and Practice of Solid-Phase Peptide Synthesis

2002 ◽  
Author(s):  
Gregg B. Fields ◽  
Janelle L Lauer-Fields
Keyword(s):  
Amino Acid ◽  
Chemical Synthesis ◽  
Protease Inhibitors ◽  
Solid Phase ◽  
Building Blocks ◽  
Pharmaceutical Products ◽  
New Drugs ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Functional Roles

Peptides play key structural and functional roles in biochemistry, pharmacology, and neurobiology, and are important probes for research in enzymology, immunology, and molecular biology. The amino acid building blocks can be among the 20 genetically encoded L-residues, or else unusual ones, and the sequences can be linear, cyclic, or branched. It follows that rapid, efficient, and reliable methodology for the chemical synthesis of these molecules is of utmost interest. A number of synthetic peptides are significant commercial or pharmaceutical products, ranging from the sweet dipeptide L-Asp-L-Phe-OMe (aspartame) to clinically used hormones such as oxytocin, adrenocorticotropic hormone, calcitonin, and gonadotropin releasing hormone (GnRH) super-agonists. Synthesis can lead to potent and selective new drugs by judicious substitutions that change functional groups and/or conformations of the parent peptide. These include introduction of N- or C-alkyl substituents, unnatural or D-amino acids, side-chain modifications including sulfate or phosphate groups or carbohydrate moieties, and constraints such as disulfide bridges between half-cystines or side-chain lactams between Lys and Asp or Glu. Commercially important products that evolved from such studies include protease inhibitors, such as captopril and other angiotensin converting enzyme (ACE) inhibitors, peptidomimetic HIV protease inhibitors, and the somatostatin analog lanreotide. Most of the biologically or medicinally important peptides which are the targets for useful structure-function studies by chemical synthesis comprise under 50 amino acid residues, but occasionally a synthetic approach can lead to important conclusions about small proteins (full or domains) in the 100-200 residue size range. Methods for synthesizing peptides are divided conveniently into two categories: solution (classical) and solid-phase pep tide synthesis (SPPS). The classical methods have evolved since the beginning of the twentieth century, and they are described amply in several reviews and books (Wünsch, 1974; Finn and Hofmann, 1976; Bodanszky and Bodanszky, 1984; Goodman et al, 2001). The solid-phase alternative was conceived and elaborated by R. B. Merrifield beginning in 1959, and has also been covered comprehensively (Erickson and Merrifield, 1976; Birr, 1978; Barany and Merrifield, 1979; Stewart and Young, 1984; Merrifield, 1986; Barany et al., 1987, 1988; Kent, 1988; Atherton and Sheppard, 1989; Fields and Noble, 1990; Barany and Albericio, 1991; Fields et al., 1992; Gutte, 1995; Fields, 1997; Lloyd-Williams et al., 1997; Chan and White, 2000; Kates and Albericio, 2000).

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