title: Introduction of alpha-hydroxymethyamino acid residues in substrate specificity P1 position of trypsin inhibitor SFTI-1 from sunflower seeds retains its activity.
abstract: In many complexes formed by serine proteinases and their inhibitors, the hydroxyl group provided by water molecule or by the inhibitor Ser residue is located close to the inhibitor P1-P1' reactive site. In order to investigate the role of this group, we synthesized analogues of trypsin inhibitor SFTI-1 isolated from the seeds of sunflower modified in P1 by alpha-hydroxymethylserine (HmSer) and both enantiomers of alpha-hydroxymethylvaline (HmVal). All the synthesized analogues inhibited bovine beta-trypsin and human leukocyte elastase. SFTI-1 analogues with HmVal and HmSer appear to be potent inhibitors of bovine beta-trypsin, whereas [Val5]SFTI-1 is practically inactive. Also trypsin inhibitory activity of [Ser5]SFTI-1 is significantly lower. Since the electrostatic interaction between protonated epsilon-NH2 group of the inhibitor P1 position and beta-carboxylate of trypsin Asp189 is the main driving force for interaction of both molecules, the results obtained are very interesting. We believe that these SFTI-1 analogues belong to a novel class of serine proteinase inhibitors.
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Zabłotna
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kret
authors.forename: Anna
authors.initials: A
authors.lastname: Jaśkiewicz
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Olma
authors.forename: Mirosław T
authors.initials: MT
authors.lastname: Leplawy
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Rolka
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D001665:Binding Sites; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006368:Helianthus / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase / Q000737:chemistry; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012639:Seeds; D012694:Serine / Q000031:analogs & derivatives / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D055672:Static Electricity; D013237:Stereoisomerism; D013379:Substrate Specificity; D014357:Trypsin / Q000737:chemistry; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D010455:Peptides; D010456:Peptides, Cyclic; C448501:SFTI-1 peptide, sunflower; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D001224:Aspartic Acid; C035563:2-methylserine; D012694:Serine; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase; D014357:Trypsin