pepstatin has been researched along with statine* in 11 studies
11 other study(ies) available for pepstatin and statine
Article | Year |
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Grassystatins D-F, Potent Aspartic Protease Inhibitors from Marine Cyanobacteria as Potential Antimetastatic Agents Targeting Invasive Breast Cancer.
Three new modified peptides named grassystatins D-F (1-3) were discovered from a marine cyanobacterium from Guam. Their structures were elucidated using NMR spectroscopy and mass spectrometry. The hallmark structural feature in the peptides is a statine unit, which contributes to their aspartic protease inhibitory activity preferentially targeting cathepsins D and E. Grassystatin F (3) was the most potent analogue, with IC Topics: Amino Acids; Aspartic Acid Proteases; Cathepsin D; Cathepsin E; Cathepsin L; Cyanobacteria; Dose-Response Relationship, Drug; Endopeptidases; Female; Guam; Humans; Inhibitory Concentration 50; Lysosomes; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Peptides; Plasminogen Activator Inhibitor 1; Protease Inhibitors | 2017 |
Diastereoselective Synthesis and Conformational Analysis of (2R)- and (2S)-Fluorostatines: An Approach Based on Organocatalytic Fluorination of a Chiral Aldehyde.
Stereoselectively fluorinated analogues of the amino acid statine have been efficiently synthesized. The key step is an organocatalytic electrophilic fluorination of a chiral β-oxygenated aldehyde, which provided a test of both diastereoselectivity and chemoselectivity. The target statine analogues were found to adopt unique conformations influenced by the fluorine gauche effect, rendering them potentially valuable building blocks for incorporation into bioactive peptides. Topics: Aldehydes; Amino Acids; Catalysis; Fluorine; Halogenation; Hydrocarbons, Fluorinated; Magnetic Resonance Spectroscopy; Molecular Conformation; Molecular Structure; Pepstatins; Stereoisomerism | 2016 |
Lower homologues of ahpatinin, aspartic protease inhibitors, from a marine Streptomyces sp.
Two linear peptides, ahpatinin Ac (1) and ahpatinin Pr (2), were isolated together with the known ahpatinin (i)Bu, pepstatin Ac, pepstatin Pr, and pepsinostreptin from a Streptomyces sp. derived from a deep-sea sediment. The structure of ahpatinin Pr (2) was assigned by interpretation of NMR data and HPLC analysis of the hydrolysate after converting to the DNP-L-Val derivative. During the LCMS analysis of the acid hydrolysate, products arising from the retro-aldol cleavage of the statine and Ahppa units in 2 were observed and could facilitate the determination of the absolute configuration of the statine class of nonproteinogenic amino acids. Both ahpatinin Ac (1) and ahpatinin Pr (2) potently inhibited pepsin and moderately inhibited cathepsin B. Topics: Amino Acids; Aspartic Acid Endopeptidases; Cathepsin B; Marine Biology; Molecular Structure; Oligopeptides; Pepsin A; Pepstatins; Protease Inhibitors; Streptomyces; Structure-Activity Relationship | 2014 |
Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation.
In our efforts to explore marine cyanobacteria as a source of novel bioactive compounds, we discovered a statine unit-containing linear decadepsipeptide, grassystatin A (1), which we screened against a diverse set of 59 proteases. We describe the structure determination of 1 and two natural analogues, grassystatins B (2) and C (3), using NMR, MS, and chiral HPLC techniques. Compound 1 selectively inhibited cathepsins D and E with IC(50)s of 26.5 nM and 886 pM, respectively. Compound 2 showed similar potency and selectivity against cathepsins D and E (IC(50)s of 7.27 nM and 354 pM, respectively), whereas the truncated peptide analogue grassystatin C (3), which consists of two fewer residues than 1 and 2, was less potent against both but still selective for cathepsin E. The selectivity of compounds 1-3 for cathepsin E over D (20-38-fold) suggests that these natural products may be useful tools to probe cathepsin E function. We investigated the structural basis of this selectivity using molecular docking. We also show that 1 can reduce antigen presentation by dendritic cells, a process thought to rely on cathepsin E. Topics: Amino Acids; Animals; Antigen Presentation; Cathepsin E; Cell Line, Tumor; Cyanobacteria; Dendritic Cells; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Oceans and Seas; Oligopeptides; Protease Inhibitors; Spectrometry, Mass, Electrospray Ionization; Substrate Specificity | 2009 |
Investigation of the synthetic route to pepstatin analogues by SPPS using O-protected and O-unprotected statine as building blocks.
The synthetic route to pepstatin derivatives by a solid phase peptide synthesis using either O-protected or O-unprotected statine as a building block has been investigated. Statine was prepared according to a modified literature procedure, whereas protection of its 3-hydroxyl moiety using tert-butyldimethylsilylchloride (TBSCl) provided the novel O-TBS-protected statine building block. The O-tert-butyldimethylsilyl (TBS)-protected statine approach provides an improved synthetic strategy for the preparation of statine-containing peptides as demonstrated by the synthesis of the pepstatin analogue iva-Val-Leu-Sta-Ala-Sta. Topics: Amino Acid Sequence; Amino Acids; Chromatography, High Pressure Liquid; Fluorenes; Indicators and Reagents; Magnetic Resonance Spectroscopy; Molecular Structure; Pepstatins | 2009 |
Inhibition of cathepsin D by tripeptides containing statine analogs.
Various analogs of statine, a remarkable amino acid component of the protease inhibitor pepstatine, were synthesized and evaluated as tripeptide derivatives for their activity against cathepsin D and HIV-1 protease. Topics: Amino Acids; Cathepsin D; HIV Protease Inhibitors; Humans; Oligopeptides; Pepstatins; Protease Inhibitors; Structure-Activity Relationship; Tumor Cells, Cultured | 1999 |
Potent and selective inhibitors of an aspartyl protease-like endothelin converting enzyme identified in rat lung.
Two structurally distinct series of potent and selective inhibitors of an aspartyl protease-like endothelin converting enzyme (ECE) activity identified in the rat lung have been developed. Pepstatin A, which potently inhibits the rat lung ECE, served as the basis for the first series. Alternatively, selected renin inhibitors containing the dihydroxyethylene moiety were shown to be inhibitors of rat lung activity. Subsequent modifications improved inhibition of the rat lung ECE while eliminating renin activity. Both series of ECE inhibitors demonstrated a range of selectivity over Cathepsin D. Water-solubilizing moieties were appended onto selected compounds to facilitate in vivo testing. Partial reduction of the pressor response to exogenously administered Big ET-1 was observed with selected rat lung ECE inhibitors. Topics: Amino Acid Sequence; Amino Acids; Animals; Aspartic Acid Endopeptidases; Blood Pressure; Cathepsin D; Cell Membrane; Endothelin-Converting Enzymes; Endothelins; Humans; Lung; Metalloendopeptidases; Molecular Sequence Data; Molecular Structure; Pepstatins; Protease Inhibitors; Rats; Renin; Solubility; Structure-Activity Relationship; Water | 1993 |
Novel renin inhibitors containing analogues of statine retro-inverted at the C-termini: specificity at the P2 histidine site.
Substituted 1,3- and 1,4-diamines were prepared from epoxides derived from Boc-leucine or Boc-cyclohexylalanine. These diamines were incorporated into renin inhibitors (IC50 = 4-1500 nM) replacing the Leu-Val scissile bond in small peptide analogues of angiotensinogen. Replacement of the P2 histidine imidazole with other heterocycles maintained or enhanced binding while changing the overall basicity of the inhibitor. Finally, substitution of O-methyltyrosine for the P3 phenylalanine suppressed chymotrypsin cleavage of the P3-P2 bond. Topics: Amino Acids; Chymotrypsin; Diamines; Histidine; Humans; Renin; Structure-Activity Relationship | 1987 |
Design and synthesis of potent and specific renin inhibitors containing difluorostatine, difluorostatone, and related analogues.
Peptides that contain difluorostatine and difluorostatone residues have been shown to be potent inhibitors of the aspartyl protease renin. The readily hydrated fluoro ketone is proposed to mimic the tetrahedral intermediate that forms during the enzyme-catalyzed hydrolysis of a peptidic bond. It is suggested that the sp3-hybridized ketal acts as a transition-state analogue renin inhibitor. The fluoro ketone is shown to be a much more effective inhibitor than the corresponding nonfluorinated ketone, which acts as a pseudosubstrate. More lipophilic side chains at the P1 site can enhance the inhibitory potency of the difluorostatine analogue, but this cannot be demonstrated in the difluorostatone series. Additionally, high renin specificity has been shown for a difluorostatone-containing peptide. Topics: Amino Acids; Fluorine; Humans; Ketones; Magnetic Resonance Spectroscopy; Peptides; Renin; Structure-Activity Relationship | 1986 |
Inhibition of cathepsin D by substrate analogues containing statine and by analogues of pepstatin.
Five new cathepsin D inhibitors were synthesized and tested as inhibitors of bovine cathepsin D. The compounds were derived by replacing a Phe-Phe dipeptidyl unit of a good cathepsin D substrate, Boc-Phe-Leu-Ala-Phe-Phe-Val-Leu-OR, with statine [3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, Sta) or with Sta-Phe. The best inhibitor, Boc-Phe-Leu-Ala-(S,S)-Sta-Val-Leu-OMe, inhibited cathepsin D with a Ki value of 1.1 nM. In general, the more effective inhibitors were consistent with the proposal that statine functions as a replacement for a dipeptidyl unit. Thirty-five known pepstatin analogues also were evaluated as cathepsin D inhibitors. Substituents in the P4 and P3' positions are important for maximal inhibition of this aspartic proteinase, and the P4 substituent appears more important for inhibition of cathepsin D than for inhibition of other aspartic proteinases. Topics: Amino Acid Sequence; Amino Acids; Animals; Cathepsin D; Cattle; Indicators and Reagents; Kinetics; Oligopeptides; Pepstatins; Structure-Activity Relationship | 1986 |
Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analogue inhibitors containing a novel analogue of statine.
Analogues of the renin octapeptide substrate were synthesized in which replacement of the scissile dipeptide with (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid (statine, Sta) transformed the substrate sequence into potent, transition-state analogue, competitive inhibitors of renin. Synthesis and incorporation of the cyclohexylalanyl analogue of Sta, (3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA), gave the most potent inhibitors of renin yet reported, including N-isovaleryl-L-histidyl-L-prolyl-L-phenylalanyl-L-histidyl-ACHPA-L -leucyl-L- phenylalanyl amide [Iva-His-Pro-Phe-His-ACHPA-Leu-Phe-NH2,3], with renin inhibitions of Ki = 1.6 X 10(-10) M (human kidney renin), IC50 = 1.7 X 10(-10)M (human plasma renin), IC50 = 1.9 X 10(-9)M (dog plasma renin), and IC50 = 2.1 X 10(-8) M (rat plasma renin). This inhibitor 3, containing ACHPA, was 55-76 times more potent vs. human renin than the comparable Sta-containing inhibitor 1 and 17 times more potent vs. dog renin than 1. Inhibitor 3 lowered blood pressure in sodium-deficient dogs, with in vivo potency 19 times that shown by 1, in close agreement with the relative in vitro potencies. Structure-activity results are presented that show the minimal N-terminus for these inhibitors. An ACHPA-containing pentapeptide, N-[(ethyloxy)carbonyl]-L-phenylalanyl-L- histidyl-ACHPA-L-leucyl-L-phenylalanyl amide [Etoc-Phe-His-ACHPA-Leu-Phe-NH2,8], retained subnanomolar inhibitory potency. Molecular modelling studies are described that suggested the design of ACHPA. Topics: Amino Acids; Animals; Binding, Competitive; Blood Pressure; Chemical Phenomena; Chemistry; Dogs; Humans; Kidney; Macaca mulatta; Mice; Oligopeptides; Rabbits; Rats; Renin | 1985 |