Abstract
Research in the field of protease inhibitors is focused on obtaining potent, specific and protease-resistant inhibitors. To our knowledge, there are no reports in the literature that consider the application of N-substituted glycine residues (peptoid monomers) for the design of peptidomimetic protease inhibitors. We hereby present the chemical synthesis and kinetic properties of two new analogues of the trypsin inhibitor SFTI-1 modified at the P1 position. Substitution of Lys5 in SFTI-1 by N-(4-aminobutyl)-glycine and N-benzylglycine, which mimic Lys and Phe, respectively, made these analogues completely protease-resistant at their P1-P1' reactive sites. The analogues synthesised appeared to be potent inhibitors of bovine beta-trypsin and alpha-chymotrypsin. These noncovalent, competitive and selective peptide-peptoid hybrid (peptomeric) inhibitors might open the way to targeting unwanted proteolysis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Binding, Competitive
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Cattle
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Chymotrypsin / metabolism
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Glycine / chemistry
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Lysine / chemistry
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Membrane Proteins / chemistry*
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Membrane Proteins / metabolism
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Peptides / chemistry*
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Peptides / metabolism
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Peptoids / chemistry*
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Peptoids / metabolism
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Phenylalanine / chemistry
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Qc-SNARE Proteins
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Saccharomyces cerevisiae Proteins / chemistry*
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Saccharomyces cerevisiae Proteins / metabolism
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Serine Proteinase Inhibitors / chemistry*
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Serine Proteinase Inhibitors / metabolism
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Structure-Activity Relationship
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Trypsin / metabolism
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Trypsin Inhibitors / chemistry*
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Trypsin Inhibitors / metabolism
Substances
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Membrane Proteins
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Peptides
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Peptoids
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Qc-SNARE Proteins
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SFT1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Serine Proteinase Inhibitors
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Trypsin Inhibitors
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Phenylalanine
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Chymotrypsin
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alpha-chymotrypsin
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Trypsin
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Lysine
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Glycine