8VJP

Histidine-covalent stapled alpha-helical peptide (155H1) targeting hMcl-1

これはPDB形式変換不可エントリーです。

8VJP の概要

• エントリーDOI: 10.2210/pdb8vjp/pdb
• 分子名称: Induced myeloid leukemia cell differentiation protein Mcl-1, Histidine-covalent stapled alpha-helical peptide, (S~1~R)-3-carbamoyl-4-methoxybenzene-1-sulfinic acid, ... (5 entities in total)
• 機能のキーワード: histidine-covalent stapled alpha-helical peptides, apoptosis
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19609.36

構造登録者

Muzzarelli, K.M.,Assar, Z.,Alboreggia, G.,Pellecchia, M. (登録日: 2024-01-07, 公開日: 2024-05-15, 最終更新日: 2024-06-05)

主引用文献

Alboreggia, G.,Udompholkul, P.,Baggio, C.,Muzzarelli, K.,Assar, Z.,Pellecchia, M.
Histidine-Covalent Stapled Alpha-Helical Peptides Targeting hMcl-1.
J.Med.Chem., 67:8172-8185, 2024

PubMed Abstract: Several novel and effective cysteine targeting (Cys) covalent drugs are in clinical use. However, the target area containing a druggable Cys residue is limited. Therefore, methods for creating covalent drugs that target different residues are being looked for; examples of such ligands include those that target the residues lysine (Lys) and tyrosine (Tyr). Though the histidine (His) side chain is more frequently found in protein binding locations and has higher desirable nucleophilicity, surprisingly limited research has been done to specifically target this residue, and there are not many examples of His-targeting ligands that have been rationally designed. In the current work, we created novel stapled peptides that are intended to target hMcl-1 His 252 covalently. We describe the in vitro (biochemical, NMR, and X-ray) and cellular design and characterization of such agents. Our findings further suggest that the use of electrophiles to specifically target His residues is warranted.

PubMed: 38695666
DOI: 10.1021/acs.jmedchem.4c00277

実験手法

X-RAY DIFFRACTION (1.13 Å)