Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases

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Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases. / Knuhtsen, Astrid; Legrand, Baptiste; Van der Poorten, Olivier; Amblard, Muriel; Martinez, Jean; Ballet, Steven; Kristensen, Jesper L; Pedersen, Daniel Sejer.

In: Chemistry: A European Journal, Vol. 22, No. 39, 12.08.2016, p. 14022–14028.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Knuhtsen, A, Legrand, B, Van der Poorten, O, Amblard, M, Martinez, J, Ballet, S, Kristensen, JL & Pedersen, DS 2016, 'Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases', Chemistry: A European Journal, vol. 22, no. 39, pp. 14022–14028. https://doi.org/10.1002/chem.201602518

APA

Knuhtsen, A., Legrand, B., Van der Poorten, O., Amblard, M., Martinez, J., Ballet, S., Kristensen, J. L., & Pedersen, D. S. (2016). Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases. Chemistry: A European Journal, 22(39), 14022–14028. https://doi.org/10.1002/chem.201602518

Vancouver

Knuhtsen A, Legrand B, Van der Poorten O, Amblard M, Martinez J, Ballet S et al. Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases. Chemistry: A European Journal. 2016 Aug 12;22(39):14022–14028. https://doi.org/10.1002/chem.201602518

Author

Knuhtsen, Astrid ; Legrand, Baptiste ; Van der Poorten, Olivier ; Amblard, Muriel ; Martinez, Jean ; Ballet, Steven ; Kristensen, Jesper L ; Pedersen, Daniel Sejer. / Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases. In: Chemistry: A European Journal. 2016 ; Vol. 22, No. 39. pp. 14022–14028.

Bibtex

@article{12c0918242434a3db3165511b0185d6f,
title = "Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases",
abstract = "Protein arginine N-methyl transferases (PRMTs) belong to a family of enzymes that modulate the epigenetic code through modifications of histones. In the present study, peptides emerging from a phage display screening were modified in the search for PRMT inhibitors through substitution with non-proteinogenic amino acids, N-alkylation of the peptide backbone, and incorporation of constrained dipeptide mimics. One of the modified peptides (23) showed an increased inhibitory activity towards several PRMTs in the low μm range and the conformational preference of this peptide was investigated and compared with the original hit using circular dichroism and NMR spectroscopy. Introducing two constrained tryptophan residue mimics (l-Aia) spaced by a single amino acid was found to induce a unique turn structure stabilized by a hydrogen bond and aromatic π-stacking interaction between the two l-Aia residues.",
author = "Astrid Knuhtsen and Baptiste Legrand and {Van der Poorten}, Olivier and Muriel Amblard and Jean Martinez and Steven Ballet and Kristensen, {Jesper L} and Pedersen, {Daniel Sejer}",
note = "{\textcopyright} 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2016",
month = aug,
day = "12",
doi = "10.1002/chem.201602518",
language = "English",
volume = "22",
pages = "14022–14028",
journal = "Chemistry: A European Journal",
issn = "0947-6539",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "39",

}

RIS

TY - JOUR

T1 - Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases

AU - Knuhtsen, Astrid

AU - Legrand, Baptiste

AU - Van der Poorten, Olivier

AU - Amblard, Muriel

AU - Martinez, Jean

AU - Ballet, Steven

AU - Kristensen, Jesper L

AU - Pedersen, Daniel Sejer

N1 - © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2016/8/12

Y1 - 2016/8/12

N2 - Protein arginine N-methyl transferases (PRMTs) belong to a family of enzymes that modulate the epigenetic code through modifications of histones. In the present study, peptides emerging from a phage display screening were modified in the search for PRMT inhibitors through substitution with non-proteinogenic amino acids, N-alkylation of the peptide backbone, and incorporation of constrained dipeptide mimics. One of the modified peptides (23) showed an increased inhibitory activity towards several PRMTs in the low μm range and the conformational preference of this peptide was investigated and compared with the original hit using circular dichroism and NMR spectroscopy. Introducing two constrained tryptophan residue mimics (l-Aia) spaced by a single amino acid was found to induce a unique turn structure stabilized by a hydrogen bond and aromatic π-stacking interaction between the two l-Aia residues.

AB - Protein arginine N-methyl transferases (PRMTs) belong to a family of enzymes that modulate the epigenetic code through modifications of histones. In the present study, peptides emerging from a phage display screening were modified in the search for PRMT inhibitors through substitution with non-proteinogenic amino acids, N-alkylation of the peptide backbone, and incorporation of constrained dipeptide mimics. One of the modified peptides (23) showed an increased inhibitory activity towards several PRMTs in the low μm range and the conformational preference of this peptide was investigated and compared with the original hit using circular dichroism and NMR spectroscopy. Introducing two constrained tryptophan residue mimics (l-Aia) spaced by a single amino acid was found to induce a unique turn structure stabilized by a hydrogen bond and aromatic π-stacking interaction between the two l-Aia residues.

U2 - 10.1002/chem.201602518

DO - 10.1002/chem.201602518

M3 - Journal article

C2 - 27515561

VL - 22

SP - 14022

EP - 14028

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

SN - 0947-6539

IS - 39

ER -

ID: 164785821