Inhibiting the assembly of protein—protein interfaces

Zutshi, Reena; Brickner, Michelle; Chmielewski, Jean

doi:10.1016/s1367-5931(98)80036-7

Cited by 104 publications

(90 citation statements)

References 30 publications

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“…The compounds that induce protein interaction were called dimerizers [108][109][110]. Agents preventing this process are inhibitors of dimerization and antagonists of peptide/protein receptors [111][112][113][114][115][116][117].…”

Section: Protein-protein Interaction As Drug Target: Myth or Reality?mentioning

confidence: 99%

“…Modification of all these interactions can be employed to change cell metabolism. For example, different peptides that terminate all stages of the cascade induced by light adsorption by rhodopsin were identified [117]. There are many examples of successful design of effective nonpeptide ligands for different types of peptide(protein) receptors: vascular endothelial growth factor receptor [127], somatostatin receptor [128], neuropeptide Y receptors [129], thromboxane A2 receptor [130], protease-activated receptors [115,131,132].…”

Section: Inhibitors Of Dimerizationmentioning

confidence: 99%

“…Some proteins act as oligomer complexes, so IDs may prevent formation of the active dimer. Such inhibitors have been discovered for three HIV enzymes (protease, reverse transcriptase, invertase) [117,[139][140][141], ribonucleotide reductase [142], DNA polymerase of herpes simplex virus [143], human gluthatione reductase [144], phosphatidylinisitol 3-kinase [145] etc.…”

Section: Inhibitors Of Dimerizationmentioning

confidence: 99%

“…The activity of such inhibitors (expressed as IC 50 or K i values) vary from low nanomolar [146,147] to micromolar concentration range [117,148,149]. Using sitedirected mutagenesis or methods of combinatorial chemistry it is possible to improve inhibitory activity of peptide IDs by optimizing their amino acid composition and sequence [117,139,147,150].…”

Section: Inhibitors Of Dimerizationmentioning

confidence: 99%

“…Using sitedirected mutagenesis or methods of combinatorial chemistry it is possible to improve inhibitory activity of peptide IDs by optimizing their amino acid composition and sequence [117,139,147,150]. The peptidomimetic molecules or small organic molecules were also recognized as IDs [117,148,151,152].…”

Section: Inhibitors Of Dimerizationmentioning

confidence: 99%

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Protein‐protein interactions as a target for drugs in proteomics

et al. 2003

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Protein-protein interactions play a central role in numerous processes in the cell and are one of the main fields of functional proteomics. This review highlights the methods of bioinformatics and functional proteomics of protein-protein interaction investigation. The structures and properties of contact surfaces, forces involved in protein-protein interactions, kinetic and thermodynamic parameters of these reactions were considered. The properties of protein contact surfaces depend on their functions. The contact surfaces of permanent complexes resemble domain contacts or the protein core and it is reasonable to consider such complex formation as a continuation of protein folding. Characteristics of contact surfaces of temporary protein complexes share some similarities with active sites of enzymes. The contact surfaces of the temporary protein complexes have unique structure and properties and they are more conservative in comparison with active site of enzymes. So they represent prospective targets for a new generation of drugs. During the last decade, numerous investigations were undertaken to find or design small molecules that block protein dimerization or protein(peptide)-receptor interaction, or, on the contrary, to induce protein dimerization.

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Section: Protein-protein Interaction As Drug Target: Myth or Reality?mentioning

confidence: 99%

Section: Inhibitors Of Dimerizationmentioning

confidence: 99%

Section: Inhibitors Of Dimerizationmentioning

confidence: 99%

Section: Inhibitors Of Dimerizationmentioning

confidence: 99%

Section: Inhibitors Of Dimerizationmentioning

confidence: 99%

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Protein‐protein interactions as a target for drugs in proteomics

et al. 2003

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Uncoiling c-Jun coiled coils: Inhibitory effects of truncated Fos peptides on Jun dimerization and DNA binding in vitro

et al. 1998

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c-Jun is an oncoprotein that comprises a portion of the AP-1 transcription factor and belongs to the basic-leucine zipper (bZIP) DNA binding protein family. Using peptides derived from the leucine zipper region of Fos, we have developed agents that inhibit Jun's DNA binding in the low micromolar range. Fos peptides that were effective inhibitors in the DNA binding assay were also found to inhibit cellular Jun binding to an AP-1 site in a luciferase reporter plasmid in MCF-7 cells. Size exclusion studies confirmed that peptides that inhibit the DNA binding of Jun also inhibit its dimerization. These peptides were found to have a cytotoxic effect on the MCF-7 cell line when delivered with the transfecting agent Tfx-50, possibly due to their role as transcription factor regulators.

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Small-Molecule Inhibitors of HIV-1 Protease Dimerization Derived from Cross-Linked Interfacial Peptides

et al. 2000

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Die kleinste Struktur, die erforderlich ist, um die Dimerisierung von HIV‐1‐Protease zu inhibieren, wurde erhalten durch Entfernen einiger Reste von den N‐Termini der Peptidketten eines bekannten Inhibitors (Ki=220±10 nM), der durch Verknüpfung der N‐Termini von Peptiden aus dem Wechselwirkungsbereich der HIV‐Protease über einen Linker erhalten wurde, und anschließendes Ersetzen des Trp‐OH‐Restes gegen Phe‐NH2. Molecular‐Modeling‐Untersuchungen an der erhaltenen Struktur führten zu 1, das die HIV‐1‐Protease über einen Dissoziationsmechanismus inhibiert und damit ein idealer Ausgangspunkt für die Identifizierung noch aktiverer Reagentien ist.

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Inhibiting the assembly of protein—protein interfaces

Cited by 104 publications

References 30 publications

Protein‐protein interactions as a target for drugs in proteomics

Protein‐protein interactions as a target for drugs in proteomics

Uncoiling c-Jun coiled coils: Inhibitory effects of truncated Fos peptides on Jun dimerization and DNA binding in vitro

Small-Molecule Inhibitors of HIV-1 Protease Dimerization Derived from Cross-Linked Interfacial Peptides

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