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Targeting of a Helix-Loop-Helix Transcriptional Regulator by a Short Helical Peptide
- Source :
- ChemMedChem. 12:1497-1503
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- The Id proteins (Id1-4) are cell-cycle regulators that play a key role during development, in cancer and vascular disorders. They contain a conserved helix-loop-helix (HLH) domain that folds into a parallel four-helix bundle upon self- or hetero-association with basic-HLH transcription factors. By using such protein-protein interactions, the Id proteins inhibit cell differentiation and promote cell-cycle progression. Accordingly, their supporting role in cancer has been convincingly demonstrated, which makes these proteins interesting therapeutic targets. Herein we present a short peptide containing an (i,i+4)-lactam bridge and a hydrophobic (Φ) three-residue motif Φ(i)-Φ(i+3)-Φ(i+6), which adopts a helical conformation in water, shows Id protein binding in the low-micromolar range, penetrates into breast (MCF-7 and T47D) and bladder (T24) cancer cells, accumulates in the nucleus, and decreases cell viability to ∼50 %. Thus, this cyclopeptide is a promising scaffold for the development of Id protein binders that impair cancer cell viability.
- Subjects :
- 0301 basic medicine
Cell Survival
Cellular differentiation
Peptide
Biology
Peptides, Cyclic
Biochemistry
Protein Structure, Secondary
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Drug Discovery
Transcriptional regulation
Humans
Protein Interaction Domains and Motifs
Amino Acid Sequence
Viability assay
General Pharmacology, Toxicology and Pharmaceutics
Transcription factor
Pharmacology
chemistry.chemical_classification
Helix-Loop-Helix Motifs
Organic Chemistry
Cell Differentiation
Cell cycle
Cell biology
030104 developmental biology
Microscopy, Fluorescence
chemistry
030220 oncology & carcinogenesis
Cancer cell
MCF-7 Cells
Molecular Medicine
Alpha helix
Protein Binding
Transcription Factors
Subjects
Details
- ISSN :
- 18607179
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- ChemMedChem
- Accession number :
- edsair.doi.dedup.....736308df01c90321d6eda8803e90e492