Engineering new peptidic inhibitors from a natural chymotrypsin inhibitor.
Three model peptides of different sizes (17-24 amino acid residues) mimicking the chymotrypsin inhibitor SCGI (a peptide of 35 amino acid residues) isolated from Schistocerca gregaria were designed and prepared by convergent peptide synthesis. Selective formation of disulphide bridges in the closing step was achieved without selective protection of cysteine residues. The natural pattern of the two disulphide bridges was determined by 2D homonuclear 1H NMR techniques. All three model peptides were characterized by amino acid analysis. MS and CD spectra. Preliminary results revealed that the two smaller model peptides exhibit no Inhibitory activity, whereas the larger one shows limited inhibition of chymotrypsin.
Mucsi
Zoltán
Z
Department of Organic Chemistry, Eötvös Loránd University, Budapest, Hungary.
Perczel
András
A
Orosz
György
G
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002942:Circular Dichroism; D004220:Disulfides / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D019476:Insect Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization
D000596:Amino Acids; D004220:Disulfides; D004791:Enzyme Inhibitors; D019476:Insect Proteins; D010455:Peptides; C113210:LOC126284306 protein, Schistocerca gregaria