scholarly journals Solid Phase Assembly of Fully Protected Trinucleotide Building Blocks for Codon-Based Gene Synthesis

2019 ◽  
Vol 9 (11) ◽  
pp. 2199 ◽  
Author(s):  
Ruth Suchsland ◽  
Bettina Appel ◽  
Matthäus Janczyk ◽  
Sabine Müller
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Building Blocks ◽  
Disulfide Bridge ◽  
Solid Support ◽  
Gene Synthesis ◽  
Directed Mutagenesis ◽  
Reducing Conditions

The use of pre-formed trinucleotides, representing codons of the 20 canonical amino acids, for oligonucleotide-directed mutagenesis offers the advantage of controlled randomization and generation of “smart libraries”. We here present a method for the preparation of fully protected trinucleotides on solid phase. The key issue of our strategy is the linkage of the starting nucleoside to the solid support via a traceless disulfide linker. Upon trinucleotide assembly, the disulfide bridge is cleaved under reducing conditions, and the fully protected trinucleotide is released with a terminal 3′-OH group.

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 An aza-Diels–Alder route to quinoline-based unnatural amino acids and polypeptide surrogates

RSC Advances ◽  
2021 ◽  
Vol 11 (23) ◽  
pp. 14132-14139
Author(s):  
M. J. Umerani ◽  
H. Yang ◽  
P. Pratakshya ◽  
J. S. Nowick ◽  
A. A. Gorodetsky
Keyword(s):  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Building Blocks ◽  
Solid Support ◽  
Diels Alder

The synthesis of quinoline-based unnatural amino acids and the subsequent preparation of polypeptide surrogates from these building blocks on solid support.

scholarly journals Programmable polyproteams built using twin peptide superglues

2016 ◽  
Vol 113 (5) ◽  
pp. 1202-1207 ◽  
Author(s):  
Gianluca Veggiani ◽  
Tomohiko Nakamura ◽  
Michael D. Brenner ◽  
Raphaël V. Gayet ◽  
Jun Yan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Death ◽  
Biological Function ◽  
Solid Phase ◽  
Building Blocks ◽  
Isopeptide Bond ◽  
Cancer Cell Death ◽  
Protein Partner ◽  
Reactive Groups ◽  
Signal Activation

Programmed connection of amino acids or nucleotides into chains introduced a revolution in control of biological function. Reacting proteins together is more complex because of the number of reactive groups and delicate stability. Here we achieved sequence-programmed irreversible connection of protein units, forming polyprotein teams by sequential amidation and transamidation. SpyTag peptide is engineered to spontaneously form an isopeptide bond with SpyCatcher protein. By engineering the adhesin RrgA from Streptococcus pneumoniae, we developed the peptide SnoopTag, which formed a spontaneous isopeptide bond to its protein partner SnoopCatcher with >99% yield and no cross-reaction to SpyTag/SpyCatcher. Solid-phase attachment followed by sequential SpyTag or SnoopTag reaction between building-blocks enabled iterative extension. Linear, branched, and combinatorial polyproteins were synthesized, identifying optimal combinations of ligands against death receptors and growth factor receptors for cancer cell death signal activation. This simple and modular route to programmable “polyproteams” should enable exploration of a new area of biological space.

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.

Synthesis of Novel Oxazolyl Amino Acids and Their Use in the Parallel Synthesis of Disubstituted Oxazole Libraries

Synthesis ◽  
2018 ◽  
Vol 50 (07) ◽  
pp. 1546-1554 ◽  
Author(s):  
Adel Nefzi ◽  
Siva Murru ◽  
Ramesh Bista
Keyword(s):  
Amino Acids ◽  
Methyl Ester ◽  
Small Molecules ◽  
High Purity ◽  
Solid Phase ◽  
Building Blocks ◽  
Parallel Synthesis ◽  
General Nature

Novel chiral oxazolyl alanine and homologues are synthesized and utilized as building blocks for the solid-phase parallel synthesis of novel trifunctional oxazole small molecules in good to excellent overall yields and with high purity. The orthogonal deprotection strategy of oxazolyl amino acids, prepared from serine methyl ester and amino acids such as aspartic and glutamic acids, allows multiple sites of diversification to make a variety of pharmacologically relevant small molecules. The general nature of this approach allows the preparation of a large number of small molecules and peptidomimetics.

scholarly journals Convergent Synthesis of Thioether Containing Peptides

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 218
Author(s):  
Spyridon Mourtas ◽  
Christina Katakalou ◽  
Dimitrios Gatos ◽  
Kleomenis Barlos
Keyword(s):  
Carboxylic Acids ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Building Blocks ◽  
Solid Support ◽  
Convergent Synthesis ◽  
Fmoc Group ◽  
Synthetic Routes ◽  
Peptide Elongation

Thioether containing peptides were obtained following three synthetic routes. In route A, halo acids esterified on 2-chlorotrityl(Cltr) resin were reacted with N-fluorenylmethoxycarbonyl (Fmoc) aminothiols. These were either cleaved from the resin to the corresponding (Fmoc-aminothiol)carboxylic acids, which were used as key building blocks in solid phase peptide synthesis (SPPS), or the N-Fmoc group was deprotected and peptide chains were elongated by standard SPPS. The obtained N-Fmoc protected thioether containing peptides were then condensed either in solution, or on solid support, with the appropriate amino components of peptides. In route B, the thioether containing peptides were obtained by the reaction of N-Fmoc aminothiols with bromoacetylated peptides, which were synthesized on Cltr-resin, followed by removal of the N-Fmoc group and subsequent peptide elongation by standard SPPS. In route C, the thioether containing peptides were obtained by the condensation of a haloacylated peptide synthesized on Cltr-resin and a thiol-peptide synthesized either on 4-methoxytrityl(Mmt) or trityl(Trt) resin.

Arylboronate Ester Protected Amino Acids as Orthogonal Building Blocks for Fmoc Solid-Phase Peptide Synthesis

2017 ◽  
Vol 2017 (39) ◽  
pp. 5916-5920 ◽  
Author(s):  
Chao Liu ◽  
Yan Zou ◽  
Hui Song ◽  
Yuan-Ye Jiang ◽  
Hong-Gang Hu
Keyword(s):  
Amino Acids ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Building Blocks
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