8VJP
Histidine-covalent stapled alpha-helical peptide (155H1) targeting hMcl-1
This is a non-PDB format compatible entry.
Summary for 8VJP
| Entry DOI | 10.2210/pdb8vjp/pdb |
| Descriptor | 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) |
| Functional Keywords | histidine-covalent stapled alpha-helical peptides, apoptosis |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 19609.36 |
| Authors | Muzzarelli, K.M.,Assar, Z.,Alboreggia, G.,Pellecchia, M. (deposition date: 2024-01-07, release date: 2024-05-15, Last modification date: 2024-06-05) |
| Primary citation | 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 Cited by 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: 38695666DOI: 10.1021/acs.jmedchem.4c00277 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.13 Å) |
Structure validation
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