Thioether Macrocyclic Peptides Selected against TET1 Compact Catalytic Domain Inhibit TET1 Catalytic Activity

Nishio, Kosuke; Belle, Roman; Katoh, Takayuki; Kawamura, Akane; Sengoku, Toru; Hanada, Kazuharu; Ohsawa, Noboru; Shirouzu, Mikako; Yokoyama, Shigeyuki; Suga, Hiroaki

doi:10.1002/cbic.201800047

Cited by 18 publications

(17 citation statements)

References 51 publications

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“…Binder [24] Ten-eleven translocation 1 TET1 mRNA TiP1 Active site inhibitor [57] Tobacco Etch Virus protease TEV phage CycTev1/2 Binder [36] Transforming growth factor-β 1-stimulated clone 22 homologous gene-1…”

Section: Cp2f-3 Cp2rmentioning

confidence: 99%

Structural diversity inde novocyclic peptide ligands from genetically encoded library technologies

et al. 2020

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Cyclic peptides discovered by genetically encoded library technologies have emerged as a class of promising molecules in chemical biology and drug discovery. Here we review the cyclic peptides identified through these techniques reported in the period 2015 to 2019, with a particular focus on the three‐dimensional structures that peptides adopt when binding to their targets. A range of different structures have been revealed through co‐crystal structures, highlighting how versatile and adaptable these molecules are in binding to diverse protein targets, such as enzymes and receptors, or challenging shallow surfaces involved in protein‐protein interfaces. Analysis of the properties of the peptides reported shows some interesting trends, with further insight for those with structural information suggestive that larger peptides are more likely to adopt secondary structure. We highlight examples where co‐crystal structures have informed the key interactions that promote high affinity and selectivity of cyclic peptides against their targets, identified novel inhibitor binding sites, and provided new insights into the biology of their targets. The structure‐guided modifications have also aided the design of cyclic peptides with improved activity and physicochemical properties. These examples highlight the importance of crystallography in future cyclic peptide drug discovery initiatives.

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Section: Cp2f-3 Cp2rmentioning

confidence: 99%

Structural diversity inde novocyclic peptide ligands from genetically encoded library technologies

et al. 2020

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“…Indeed, Suga et al developed an mRNA display-based selection method, referred to as the Random nonstandard Peptides Integrated Discovery system, which enables the selection of peptides containing nPAAs using a reprogrammed genetic code with flexizyme-charged nPAA-tRNAs. Such systems provide a good drug-discovery platform for the development of structurally unique peptide ligands containing nPAAs [44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61].…”

Section: Perspectivesmentioning

confidence: 99%

Engineering Translation Components Improve Incorporation of Exotic Amino Acids

Katoh¹,

Suga²

2019

IJMS

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Methods of genetic code manipulation, such as nonsense codon suppression and genetic code reprogramming, have enabled the incorporation of various nonproteinogenic amino acids into the peptide nascent chain. However, the incorporation efficiency of such amino acids largely varies depending on their structural characteristics. For instance, l-α-amino acids with artificial, bulky side chains are poorer substrates for ribosomal incorporation into the nascent peptide chain, mainly owing to the lower affinity of their aminoacyl-tRNA toward elongation factor-thermo unstable (EF-Tu). Phosphorylated Ser and Tyr are also poorer substrates for the same reason; engineering EF-Tu has turned out to be effective in improving their incorporation efficiencies. On the other hand, exotic amino acids such as d-amino acids and β-amino acids are even poorer substrates owing to their low affinity to EF-Tu and poor compatibility to the ribosome active site. Moreover, their consecutive incorporation is extremely difficult. To solve these problems, the engineering of ribosomes and tRNAs has been executed, leading to successful but limited improvement of their incorporation efficiency. In this review, we comprehensively summarize recent attempts to engineer the translation systems, resulting in a significant improvement of the incorporation of exotic amino acids.

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“…Steady state kinetic analysis of TET2CD(delD1099-1936) using LC-MS/MS revealed the affinities of modified cytosine to reduce with increasing oxidation (KM = 0.48, 0.9 and 1.3 µM for 5mC, 5hmC and 5fC respectively) [118]. Assays using antibodies against modified cytosines, such as enzymelinked immunosobent assay (ELISA) and AlphaScreen, have also helped improve the sensitivity, the volumes and throughput of the assays [158]. Assays using radiolabelling (e.g.…”

Section: Kinetic Analysis Of Human Tetsmentioning

confidence: 99%

“…We have recently reported the development of macrocyclic peptide inhibitors for the human TETs [158]. Using mRNA-display based RaPID technology, macrocyclic peptide binders of human TET1CD delD1099-1936 were selected from a pool of >10 12 peptides.…”

Section: Non-metal Chelating Inhibitors Of Tetsmentioning

confidence: 99%

Chemical Compounds Targeting DNA Methylation and Hydroxymethylation

Belle

Kawamura

Arimondo

2019

Topics in Medicinal Chemistry

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DNA methylation and its oxidised forms participate in the interpretation and regulation of the human genome. Many questions arise around the enzymes responsible of these chemical modifications of DNA and their roles in regulating these modifications, which are very dynamic but are specific in the location and context (tissues, diseases, etc.). We reviewed here the major enzymes involved in DNA methylation and oxidation, with a focus on the DNA methyltransferases and TET enzymes. The principal compounds that inhibit these enzymes are presented since they will help address these questions.

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Thioether Macrocyclic Peptides Selected against TET1 Compact Catalytic Domain Inhibit TET1 Catalytic Activity

Cited by 18 publications

References 51 publications

Structural diversity inde novocyclic peptide ligands from genetically encoded library technologies

Structural diversity inde novocyclic peptide ligands from genetically encoded library technologies

Engineering Translation Components Improve Incorporation of Exotic Amino Acids

Chemical Compounds Targeting DNA Methylation and Hydroxymethylation

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