Site-specific methylation on α-N-terminus of peptides through chemical and enzymatic methods

Ying Meng; Rong Huang

doi:10.1016/bs.mie.2023.02.008

Site-specific methylation on α-N-terminus of peptides through chemical and enzymatic methods

Methods Enzymol. 2023:684:113-133. doi: 10.1016/bs.mie.2023.02.008. Epub 2023 Mar 24.

Authors

Ying Meng¹, Rong Huang²

Affiliations

¹ Department of Medicinal Chemistry and Molecular Pharmacology, Purdue Institute for Drug Discovery, Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, United States.
² Department of Medicinal Chemistry and Molecular Pharmacology, Purdue Institute for Drug Discovery, Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN, United States. Electronic address: huang-r@purdue.edu.

Abstract

Protein α-N-terminal (Nα) methylation is a post-translational modification catalyzed by N-terminal methyltransferase 1/2 (NTMT1/2) and METTL13. Nα methylation affects protein stability, protein-protein interaction, and protein-DNA interaction. Thus, Nα methylated peptides are essential tools to study the function of Nα methylation, generate specific antibodies for different states of Nα methylation, and characterize the enzyme kinetics and activity. Here, we describe chemical methods of site-specific synthesis of Nα mono-, di-, and trimethylated peptides in the solid phase. In addition, we describethe preparation of trimethylation peptides by recombinant NTMT1 catalysis.

Keywords: Methyltransferase; Nα methylated peptides; Nα methylation; Site-specific methylation.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Methylation
Peptides* / chemistry
Protein Processing, Post-Translational*

Substances

Peptides

Grants and funding

R01 GM117275/GM/NIGMS NIH HHS/United States