Journal: Chembiochem

Article Title: Structural Studies Provide New Insights into the Role of Lysine Acetylation on Substrate Recognition by CARM1 and Inform the Design of Potent Peptidomimetic Inhibitors

doi: 10.1002/cbic.202100506

Figure Lengend Snippet: A) CARM1 active site with key active residues interacting with cofactor SAM and the target arginine of a peptide substrate. The double E‐loop consists of glutamate residues Glu 258 and Glu 267 . His 415 is involved in substrate recognition as part of the THW‐loop and interacts with Asp 166 for the deprotonation of the guanidine moiety facilitating methyl group transfer. B) Design strategy used in preparing bi‐substrate analogues for structural studies and peptidic inhibitors of CARM1.

Article Snippet: The commercially available PRMT1 and CARM1 chemiluminescent assay kits (BPS Bioscience, Dan Diego, CA, USA) were used for evaluation of methyltransferase inhibition as previously described.

Techniques:

Journal: Chembiochem

Article Title: Structural Studies Provide New Insights into the Role of Lysine Acetylation on Substrate Recognition by CARM1 and Inform the Design of Potent Peptidomimetic Inhibitors

doi: 10.1002/cbic.202100506

Figure Lengend Snippet: General synthetic scheme for the preparation of transition state peptidomimetics with the adenosine moiety covalently linked to the side chain of the CARM1 target arginine. Also indicated is the neighbouring lysine residue in either acetylated or nonacetylated state. Details of the synthesis of the specific H3 peptidomimetics prepared as well as the preparation of the Pbf‐protected adenosine thiourea building block are provided in the Supporting Information.

Article Snippet: The commercially available PRMT1 and CARM1 chemiluminescent assay kits (BPS Bioscience, Dan Diego, CA, USA) were used for evaluation of methyltransferase inhibition as previously described.

Techniques: Blocking Assay

Journal: Chembiochem

Article Title: Structural Studies Provide New Insights into the Role of Lysine Acetylation on Substrate Recognition by CARM1 and Inform the Design of Potent Peptidomimetic Inhibitors

doi: 10.1002/cbic.202100506

Figure Lengend Snippet: Electron density (2 F obs‐ F calc) weighted maps for subunit A of mmCARM1 bound to: A) peptidomimetic 3 (H3 13–31 Lys 18 −NH 2 ), PDB code 7OS4 and B) peptidomimetic 4 (H3 13–31 Lys 18 Ac), PDB code 7OKP. CARM1 is represented as cartoon and H3 peptidomimetics are represented as stick. Maps are represented as a mesh contouring level set to 1σ.

Article Snippet: The commercially available PRMT1 and CARM1 chemiluminescent assay kits (BPS Bioscience, Dan Diego, CA, USA) were used for evaluation of methyltransferase inhibition as previously described.

Techniques:

Journal: Chembiochem

Article Title: Structural Studies Provide New Insights into the Role of Lysine Acetylation on Substrate Recognition by CARM1 and Inform the Design of Potent Peptidomimetic Inhibitors

doi: 10.1002/cbic.202100506

Figure Lengend Snippet: IC 50 values and for compounds 5–14 against CARM1 and PRMT1. [a]

Article Snippet: The commercially available PRMT1 and CARM1 chemiluminescent assay kits (BPS Bioscience, Dan Diego, CA, USA) were used for evaluation of methyltransferase inhibition as previously described.

Techniques: Sequencing

Journal: Chembiochem

Article Title: Structural Studies Provide New Insights into the Role of Lysine Acetylation on Substrate Recognition by CARM1 and Inform the Design of Potent Peptidomimetic Inhibitors

doi: 10.1002/cbic.202100506

Figure Lengend Snippet: IC 50 values and for compounds 5–14 against CARM1 and PRMT1. [a]

Article Snippet: The commercially available PRMT1 and CARM1 chemiluminescent assay kits (BPS Bioscience, Dan Diego, CA, USA) were used for evaluation of methyltransferase inhibition as previously described.

Techniques: Sequencing