The discovery of a freezing-induced peptide ligation during the total chemical synthesis of human interferon-ε

2018 ◽  
Vol 16 (28) ◽  
pp. 5097-5101
Author(s):  
Yin-He Yang ◽  
Bin Di ◽  
Da-Song Yang
Keyword(s):  
Amino Acids ◽  
Chemical Synthesis ◽  
Hiv Infection ◽  
Total Synthesis ◽  
Human Interferon ◽  
Peptide Ligation

The first example of a counterintuitive freezing-induced peptide ligation was discovered during the total synthesis of human interferon-ε (187 amino acids) which blocks HIV infection through unique mechanisms.

Computationally Augmented Retrosynthesis: Total Synthesis of Paspaline A and Emindole PB

2018 ◽  
Author(s):  
Timothy Newhouse ◽  
Daria E. Kim ◽  
Joshua E. Zweig
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Small Molecules ◽  
First Principles ◽  
Quantum Chemical ◽  
Computational Analysis ◽  
Empirical Evaluation ◽  
Synthetic Strategy ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

The diverse molecular architectures of terpene natural products are assembled by exquisite enzyme-catalyzed reactions. Successful recapitulation of these transformations using chemical synthesis is hard to predict from first principles and therefore challenging to execute. A means of evaluating the feasibility of such chemical reactions would greatly enable the development of concise syntheses of complex small molecules. Herein, we report the computational analysis of the energetic favorability of a key bio-inspired transformation, which we use to inform our synthetic strategy. This approach was applied to synthesize two constituents of the historically challenging indole diterpenoid class, resulting in a concise route to (–)-paspaline A in 9 steps from commercially available materials and the first pathway to and structural confirmation of emindole PB in 13 steps. This work highlights how traditional retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.

Probing the SAR of dEpoB via Chemical Synthesis:  A Total Synthesis Evaluation of C26-(1,3-dioxolanyl)-12,13-desoxyepothilone B

2002 ◽  
Vol 67 (22) ◽  
pp. 7730-7736 ◽  
Author(s):  
Mark D. Chappell ◽  
Christina R. Harris ◽  
Scott D. Kuduk ◽  
Aaron Balog ◽  
Zhicai Wu ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis

scholarly journals New cyclization reactions in organic syntheses

2002 ◽  
Vol 74 (1) ◽  
pp. 159-166 ◽  
Author(s):  
Iwao Ojima
Keyword(s):  
Amino Acids ◽  
Transition Metal ◽  
Total Synthesis ◽  
Cyclization Reactions ◽  
Organic Syntheses ◽  
Carbocyclic Compounds ◽  
Efficient Construction ◽  
Transition Metal Catalyzed ◽  
Metal Catalyzed

Recent development in the transition metal-catalyzed cyclization reactions for organic syntheses in the author's laboratories is summarized, which includes (i) novel silylcarbocyclizations (SiCaCs) and carbonylative carbotricyclizations, (ii) intramolecular silylformylations and desymmerization of siloxydiynes by sequential double silylformylation, (iii) efficient total synthesis of (+)-prosopinine, (iv) enantioselective desymmetrization of aminodienes, and (iv) new and efficient routes to 1-azabicyclo[x.y.0]alkane amino acids. All these processes are catalyzed by Rh or Rh­Co complexes, and useful for rapid and efficient construction of a variety of heterocyclic and carbocyclic compounds. Mechanisms of these new carbocyclization and cyclohydrocarbonylation reactions are also discussed.

scholarly journals Chemical synthesis and enzymatic, stereoselective hydrolysis of a functionalized dihydropyrimidine for the synthesis of β-amino acids

AMB Express ◽  
2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Christin Slomka ◽  
Sabilla Zhong ◽  
Anna Fellinger ◽  
Ulrike Engel ◽  
Christoph Syldatk ◽  
...  
Keyword(s):  
Amino Acids ◽  
Chemical Synthesis ◽  
Stereoselective Hydrolysis ◽  
Hydrolysis Of

scholarly journals A Straightforward Methodology to Overcome Solubility Challenges for N-Terminal Cysteinyl Peptide Segments Used in Native Chemical Ligation

2020 ◽  
Author(s):  
Skander Abboud ◽  
El hadji Cisse ◽  
Michel Doudeau ◽  
Hélène Bénédetti ◽  
Vincent AUCAGNE
Keyword(s):  
Amino Acids ◽  
Chemical Synthesis ◽  
Building Blocks ◽  
Native Chemical Ligation ◽  
Synthetic Approach ◽  
Chemical Ligation ◽  
Limited Solubility ◽  
Peptide Segments

One of the main limitations encountered during the chemical synthesis of proteins through native chemical ligation (NCL) is the limited solubility of some of the peptide segments. The most commonly used solution to overcome this problem is to derivatize the segment with a temporary solubilizing tag. Conveniently, the tag can be introduced on the thioester segment in such a way that it is removed concomitantly with the NCL reaction. We herein describe a generalization of this approach to N-terminal cysteinyl segment counterparts, using a straightforward synthetic approach that can be easily automated from commercially available building blocks, and applied it to a well-known problematic target, SUMO-2 (93 amino acids).

scholarly journals The viral set point in primary HIV infection is associated with specific amino acids in position 97 of MHC class I

Retrovirology ◽  
2012 ◽  
Vol 9 (S2) ◽  
Author(s):  
SA Vaidya ◽  
H Streeck ◽  
F Pereyra ◽  
ES Rosenberg ◽  
BD Walker ◽  
...  
Keyword(s):  
Amino Acids ◽  
Hiv Infection ◽  
Mhc Class I ◽  
Class I ◽  
Set Point ◽  
Primary Hiv Infection

scholarly journals Synthesis of proteins by automated flow chemistry

Science ◽  
2020 ◽  
Vol 368 (6494) ◽  
pp. 980-987 ◽  
Author(s):  
N. Hartrampf ◽  
A. Saebi ◽  
M. Poskus ◽  
Z. P. Gates ◽  
A. J. Callahan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Chemical Synthesis ◽  
Flow Chemistry ◽  
Chain Elongation ◽  
High Fidelity ◽  
Structural Units ◽  
Regulatory Factors ◽  
Synthetic Materials ◽  
Consecutive Reactions ◽  
Fast Flow

Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. Here, we report highly efficient chemistry matched with an automated fast-flow instrument for the direct manufacturing of peptide chains up to 164 amino acids long over 327 consecutive reactions. The machine is rapid: Peptide chain elongation is complete in hours. We demonstrate the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials display biophysical and enzymatic properties comparable to the biologically expressed proteins. High-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome.

ChemInform Abstract: Stereoselective Total Synthesis of Topographically Constrained Designer Amino Acids: 2′,6′-Dimethyl-β-methyltyrosines.

ChemInform ◽  
2010 ◽  
Vol 26 (29) ◽  
pp. no-no
Author(s):  
X. QIAN ◽  
K. C. RUSSELL ◽  
L. W. BOTEJU ◽  
V. J. HRUBY
Keyword(s):  
Amino Acids ◽  
Total Synthesis
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