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Bivalent inhibition of β-Tryptase: distance scan of neighboring subunits by dibasic inhibitors
- Source :
- Bioorganic & Medicinal Chemistry Letters. 12:985-988
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- Based on bifunctional diketopiperazines as templates and m-aminomethyl-phenylalanine as arginine mimetic, we have synthesized a new class of structurally related dibasic tryptase inhibitors with systematically increasing spacer length. These compounds were used to scan the distance between the active sites of two neighboring subunits of the beta-tryptase tetramer. The K(i)-values obtained are a function of the distance between the terminal amino groups and indicate optimal binding of inhibitors with 29-31 bonds between the amino groups. These experimental data are in full agreement with predictions derived from a novel modeling program that allows the docking of bivalent ligands.
- Subjects :
- Models, Molecular
Molecular model
Stereochemistry
Clinical Biochemistry
Pharmaceutical Science
Peptide
Ligands
Biochemistry
chemistry.chemical_compound
Tetramer
Drug Discovery
Humans
Enzyme Inhibitors
Bifunctional
Molecular Biology
Diketopiperazines
chemistry.chemical_classification
Dipeptide
Dibasic acid
Serine Endopeptidases
Organic Chemistry
chemistry
Docking (molecular)
Molecular Medicine
Tryptases
Algorithms
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....3ea019fd335d7edc89faab23f1aab83f