Delving into the Latest Updates on Arris Pharmaceutical Corp. with Synapse

Overview

AbstractHuman tissue kallikrein, a trypsin‐like serine protease involved in blood pressure regulation and inflammation processes, was expressed in a deglycosylated form at high levels in Pichia pastoris, purified, and crystallized. The crystal structure at 2.0 Å resolution is described and compared with that of porcine kallikrein and of other trypsin‐like proteases. The active and S1 sites (nomenclature of Schechter I, Berger A, 1967, Biochem Biophys Res Commun 27:157‐162) are similar to those of porcine kallikrein. Compared to trypsin, the S1 site is enlarged owing to the insertion of an additional residue, cis‐Pro 219. The replacement Tyr 228 → Ala further enlarges the S1 pocket. However, the replacement of Gly 226 in trypsin with Ser in human tissue kallikrein restricts accessibility of substrates and inhibitors to Asp 189 at the base of the S1 pocket; there is a hydrogen bond between Oδ1Asp189 and Oγser226. These changes in the architecture of the S1 site perturb the binding of inhibitors or substrates from the modes determined or inferred for trypsin. The crystal structure gives insight into the structural differences responsible for changes in specificity in human tissue kallikrein compared with other trypsin‐like proteases, and into the structural basis for the unusual specificity of human tissue kallikrein in cleaving both an Arg‐Ser and a Met‐Lys peptide bond in its natural protein substrate, kininogen. A Zn+2‐dependent, small‐molecule competitive inhibitor of kallikrein (Ki = 3.3 μM) has been identified and the bound structure modeled to guide drug design.

01 Mar 1998·American Journal of Rhinology

Effect of Recombinant Neutral Endopeptidase (EC 3.4.24.11) on Neuropeptide-Mediated Nasal Fluid Secretion and Plasma Exudation in the Rat

Article

Author: Stroman, Fritz ; Petersson, Göran ; Becker, Magnus ; Brenner, Daniel G. ; Josefsson, Malin

The nasal mucosa harbors sensory nerves containing neuropeptides such as substance P (SP), which are released by capsaicin. The neuropeptides are degraded by peptidases, e.g., neutral endopeptidase (NEP) that is present in the nasal mucosa. We studied the effect of enzymatically active recombinant NEP (rNEP) on neuropeptide-evoked secretion of nasal fluid and plasma exudation in rats. rNEP administered intranasally (i.n.) reduced the capsaicin-evoked nasal fluid secretion but failed to reduce the secretion evoked by SP (exogenous) under the experimental conditions used. rNEP reduced the increase in nasal plasma exudation evoked by capsaicin (endogenous neuropeptides). Because rNEP reduced neuropeptide-mediated nasal fluid secretion and plasma exudation in the rat, we suggest that peptidase activity in the nasal mucosa will determine the magnitude of the response to locally released neuropeptides.

01 Apr 1996·Biochemical JournalQ3 · BIOLOGY

Peptidyl vinyl sulphones: a new class of potent and selective cysteine protease inhibitors: S2P2 specificity of human cathepsin O2 in comparison with cathepsins S and L

Q3 · BIOLOGY

Article

Author: Okamoto, K ; Klaus, J L ; Palmer, J T ; Brömme, D ; Rasnick, D

Peptidyl vinyl sulphones are a novel class of extremely potent and specific cysteine protease inhibitors. They are highly active against the therapeutically important cathepsins O2, S and L. The highest kinact/Ki values exceed 107 M-1·s-1 for cathepsin S and 105 M-1·s-1 for cathepsins O2 and L. To study the primary specificity site of the novel human cathepsin O2 and the effectiveness of this novel class of inhibitors, a series of peptidyl vinyl sulphones with variations in the P2 residue was synthesized. Leucine in the P2 position was proven to be the most effective residue for cathepsin O2 and also for cathepsins S and L. Cathepsins O2 and S share a decreased accessibility towards P2 hydrophobic non-branched residues such as aminohexanoic acid (norleucine), methionine and oxidized methionine, but are distinguished by their different affinity towards phenylalanine in the P2 position. In contrast, cathepsin S accepts a broader range of hydrophobic residues in its S2 subsite than cathepsins O2 and L. The primary specificity-determining subsite pocket S2 in cathepsin O2 appears to be spatially more restricted than those of cathepsins S and L.

100 Deals associated with Arris Pharmaceutical Corp.

Login to view more data

100 Translational Medicine associated with Arris Pharmaceutical Corp.

Login to view more data

Corporation Tree

Boost your research with our corporation tree data.

login

or

view full example data

Boost your research with our corporation tree data.

Pipeline

Pipeline Snapshot as of 15 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Other

3

Login to view more data

Current Projects

Drug(Targets)	Indications	Global Highest Phase

APC-1390 ( Tryptase )	Asthma More	Discontinued
BAY-17-1998 ( Tryptase )	Asthma More	Discontinued
ICI-1 ( cysteine protease )	Inflammatory Bowel Diseases More	Pending