N-Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions

Authors

  • Dr. Jayanta Chatterjee,

    1. Genome biology unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg (Germany)
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    • These authors contributed equally to this work.

  • Florian Rechenmacher,

    1. Institute for Advanced Study and Center of Integrated Protein Science, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
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    • These authors contributed equally to this work.

  • Prof. Horst Kessler

    Corresponding author
    1. Institute for Advanced Study and Center of Integrated Protein Science, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
    2. Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589 (Saudi Arabia)
    • Institute for Advanced Study and Center of Integrated Protein Science, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)

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Abstract

N-Methylation is one of the simplest chemical modifications often occurring in peptides and proteins of prokaryotes and higher eukaryotes. Over years of evolution, nature has employed N-methylation of peptides as an ingenious technique to modulate biological function, often as a mode of survival through the production of antibiotics. This small structural change can not only mobilize large protein complexes (as in the histone methylation), but also inhibits the action of enzymes by selective recognition of protein–protein interaction surfaces. In recent years through the advancement in synthetic approaches, the potential of N-methylation has begun to be revealed, not only in modulating biological activity and selectivity as well as pharmacokinetic properties of peptides, but also in delivering novel drugs. Herein, we summarize the current knowledge of the versatility of N-methylation in modulating biological, structural, and pharmacokinetic properties of peptides.

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