Pentapeptides containing two dehydrophenylalanine residues--synthesis, structural studies and evaluation of their activity towards cathepsin C.
Synthesis, structural and biological studies of pentapeptides containing two DeltaPhe residues (Z and E isomers) in position 2 and 4 in peptide chain were performed. All the investigated peptides adopted bent conformation and majority of them could exist as two different conformers in solution. Only pentapeptides, containing free N-termini appeared to act as weak inhibitors of cathepsin C with the slow-binding, competitive mechanism of inhibition, free acids being bound slightly better than their methyl esters. Results of molecular modeling suggested significant difference between peptides, depending of the type of amino acid residue in position 5 in peptide chain. Dehydropeptides containing Gly residue in this position may act as competitive slow-reacting substrates and therefore exhibit inhibitory-like properties.
Latajka
R
R
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland. rafal.latajka@pwr.wroc.pl
Jewginski
M
M
Makowski
M
M
Pawełczak
M
M
Huber
T
T
Sewald
N
N
Kafarski
P
P
D001667:Binding, Competitive / Q000502:physiology; D020789:Cathepsin C / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000502:physiology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D017433:Protein Structure, Secondary; D013379:Substrate Specificity / Q000502:physiology
D009842:Oligopeptides; D011480:Protease Inhibitors; D010649:Phenylalanine; C018632:phenyldehydroalanine; D020789:Cathepsin C