Ribosomal Synthesis of Macrocyclic Peptides with Linear γ4- and β-Hydroxy-γ4-amino Acids

2021 ◽  
Author(s):  
Emel Adaligil ◽  
Aimin Song ◽  
Christian N. Cunningham ◽  
Wayne J. Fairbrother
Keyword(s):  
Amino Acids ◽  
Macrocyclic Peptides

scholarly journals Expanded toolbox for directing the biosynthesis of macrocyclic peptides in bacterial cells

2020 ◽  
Vol 11 (24) ◽  
pp. 6202-6208
Author(s):  
Jacob A. Iannuzzelli ◽  
Rudi Fasan
Keyword(s):  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Bacterial Cells ◽  
Macrocyclic Peptides ◽  
Live Bacteria

A new suite of unnatural amino acids is reported for directing the biosynthesis of genetically encoded macrocyclic peptides in live bacteria.

Novel Cylindrical, Conical, and Macrocyclic Peptides from the Cyclooligomerization of Functionalized Thiazole Amino Acids

2001 ◽  
Vol 123 (2) ◽  
pp. 333-334 ◽  
Author(s):  
Yogendra Singh ◽  
Nikolai Sokolenko ◽  
Michael J. Kelso ◽  
Lawrence R. Gahan ◽  
Giovanni Abbenante ◽  
...  
Keyword(s):  
Amino Acids ◽  
Macrocyclic Peptides

Ribosomal Synthesis of Backbone-Macrocyclic Peptides Containing γ-Amino Acids

ChemBioChem ◽  
2011 ◽  
Vol 12 (8) ◽  
pp. 1183-1187 ◽  
Author(s):  
Yukinori Ohshiro ◽  
Eiji Nakajima ◽  
Yuki Goto ◽  
Shinichiro Fuse ◽  
Takashi Takahashi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Macrocyclic Peptides

scholarly journals Cover Picture: Ribosomal Synthesis of Backbone-Macrocyclic Peptides Containing γ-Amino Acids (ChemBioChem 8/2011)

ChemBioChem ◽  
2011 ◽  
Vol 12 (8) ◽  
pp. 1137-1137
Author(s):  
Yukinori Ohshiro ◽  
Eiji Nakajima ◽  
Yuki Goto ◽  
Shinichiro Fuse ◽  
Takashi Takahashi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Macrocyclic Peptides

scholarly journals A Phage-Compatible Strategy to Access Macrocyclic Peptides Featuring Asymmetric Molecular Scaffolds as Cyclization Units

2021 ◽  
Author(s):  
Titia Rixt Oppewal ◽  
Johan Hekelaar ◽  
Clemens Mayer
Keyword(s):  
Amino Acids ◽  
Coat Protein ◽  
Phage Display ◽  
Synthetic Peptides ◽  
Cysteine Residue ◽  
Molecular Scaffolds ◽  
Noncanonical Amino Acids ◽  
Disulfide Formation ◽  
Macrocyclic Peptides ◽  
Selection Of

The cyclization of peptides appended onto proteins or whole bacteriophages is typically achieved via disulfide formation, the use of symmetric crosslinkers or the incorporation of noncanonical amino acids. Unfortunately, neither of these strategies is amenable toward generating libraries for the selection of macrocyclic peptides (MPs) akin to those found in nature, which often feature asymmetric molecular scaffolds as cyclization units that improve binding to their targets. To meet this challenge, we present an efficient two-step strategy to access MPs via the programmed modification of a unique cysteine residue and an N-terminal amine. We demonstrate that this approach yields MPs featuring asymmetric cyclization units from both synthetic peptides and when linear precursors are appended onto a phage-coat protein. Given that the employed conditions are compatible with phage display protocols, our work paves the way for the selection of natural-product-like MPs from randomized peptide sequences by phage display.

A Short and Scalable Synthesis of Orthogonally Protected Bis(aminomethyl)malonic Acid: Access to Bioactive Macrocyclic Peptides

Synthesis ◽  
2017 ◽  
Vol 49 (22) ◽  
pp. 5039-5044
Author(s):  
Muthalagu Vetrichelvan ◽  
Vijayabhaskar Bokkala ◽  
Surendran Renganathan ◽  
Arvind Mathur ◽  
Richard Rampulla ◽  
...  
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Total Synthesis ◽  
Malonic Acid ◽  
Good Yield ◽  
Building Blocks ◽  
Nucleophilic Attack ◽  
Macrocyclic Peptides ◽  
Scalable Synthesis ◽  
Key Steps

A short and scalable process for the preparation of multi-gram quantities of orthogonally protected bis(aminomethyl)malonic acid in good yield from readily available starting material is described. These orthogonally protected amino acids are important building blocks to make peptides based drugs, glycoconjugates, and in the total synthesis of peptide natural products. The newly developed route has only six steps with an overall yield of 27%, which involves nucleophilic attack of a malonate on an imide as one of the key steps.

scholarly journals Comprehensive computational design of ordered peptide macrocycles

Science ◽  
2017 ◽  
Vol 358 (6369) ◽  
pp. 1461-1466 ◽  
Author(s):  
Parisa Hosseinzadeh ◽  
Gaurav Bhardwaj ◽  
Vikram Khipple Mulligan ◽  
Matthew D. Shortridge ◽  
Timothy W. Craven ◽  
...  
Keyword(s):  
Amino Acids ◽  
Computational Models ◽  
Computational Design ◽  
Rational Drug Design ◽  
Structural Space ◽  
Rational Drug ◽  
Macrocyclic Peptides ◽  
The Rich ◽  
Hydrophobic Cores ◽  
Stable Structures

Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with l-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of l- and d-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods.

scholarly journals Ribosomal Synthesis of Macrocyclic Peptides in Vitro and in Vivo Mediated by Genetically Encoded Aminothiol Unnatural Amino Acids

2015 ◽  
Vol 10 (8) ◽  
pp. 1805-1816 ◽  
Author(s):  
John R. Frost ◽  
Nicholas T. Jacob ◽  
Louis J. Papa ◽  
Andrew E. Owens ◽  
Rudi Fasan
Keyword(s):  
Amino Acids ◽  
Unnatural Amino Acids ◽  
Macrocyclic Peptides

scholarly journals Thiazole–amino acids: influence of thiazole ring on conformational properties of amino acid residues

Amino Acids ◽  
2021 ◽  
Author(s):  
Monika Staś ◽  
Małgorzata A. Broda ◽  
Dawid Siodłak
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Dft Method ◽  
Structural Motif ◽  
Thiazole Ring ◽  
Amino Acid Residues ◽  
Conformational Preferences ◽  
Macrocyclic Peptides ◽  
Structural Database

Abstract Post-translational modified thiazole–amino acid (Xaa–Tzl) residues have been found in macrocyclic peptides (e.g., thiopeptides and cyanobactins), which mostly inhibit protein synthesis in Gram + bacteria. Conformational study of the series of model compounds containing this structural motif with alanine, dehydroalanine, dehydrobutyrine and dehydrophenylalanine were performed using DFT method in various environments. The solid-state crystal structure conformations of thiazole–amino acid residues retrieved from the Cambridge Structural Database were also analysed. The studied structural units tend to adopt the unique semi-extended β2 conformation; which is stabilised mainly by N–H⋯NTzl hydrogen bond, and for dehydroamino acids also by π-electron conjugation. The conformational preferences of amino acids with a thiazole ring were compared with oxazole analogues and the role of the sulfur atom in stabilising the conformations of studied peptides was discussed.

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