Disease relevance of Prep

• JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- phenylmethyl)-1-pyrrolidinecarboxamide) is a potent (IC50: 0.83 +/- 0.09 nM in rat brain supernatant; 5.43 +/- 0.81 nM in Flavobacterium meningosepticum) and specific inhibitor of prolyl endopeptidase (PEP) [1].
• Normalization of STZ induced hyperglycemia by sodium metavanadate treatment or by replacement of exogenous insulin did not restore pancreatic PE activity [2].
• Compound S 17092 is a potent and selective inhibitor of prolyl endopeptidase (EC 3.4.21.26, PEP) that may be of therapeutic value for the treatment of memory impairment associated with neurodegenerative diseases [3].
• We investigated the effects of the prolyl endopeptidase inhibitors 1-[1-(Benzyloxycarbonyl)-L-prolyl]prolinal (Z-Pro-Prolinal) and N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylaceta l (ZTTA) on delayed neuronal death induced by four-vessel-occlusion transient ischemia in rats [4].
• We investigated the effect of N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylaceta l (ZTTA), a novel postproline cleaving enzyme (prolyl endopeptidase, PPCE) inhibitor, on the in vitro activity of rat brain PPCE and memory impairment induced by cerebral ischemia [5].

Psychiatry related information on Prep

• In this report, the pharmacological actions of JTP-4819, a novel specific prolyl endopeptidase (PEP) inhibitor devised for the treatment of Alzheimer's disease, are reviewed with respect to its effects on PEP activity, neuropeptidergic and cholinergic neurons, and memory-related behavior in rats [6].
• Protective effect of eurystatins A and B, new prolyl endopeptidase inhibitors, on scopolamine-induced amnesia in rats [7].

High impact information on Prep

• Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on prolyl endopeptidase activity and substance P- and arginine-vasopressin-like immunoreactivity in the brains of aged rats [8].
• The degradation of thyrotropin-releasing hormone in rat brain homogenates was studied in the presence of N-benzyloxycarbonyl-prolyl-prolinal and pyroglutamyl diazomethyl ketone, specific and potent active-site-directed inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase, respectively [9].
• Delineation of a particulate thyrotropin-releasing hormone-degrading enzyme in rat brain by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase [9].
• The enzymes studied were prolyl endopeptidase (EC 3.4.21.26), a soluble metalloendopeptidase, pyroglutamyl peptide hydrolase (EC 3.4.11.8), a multicatalytic protease complex, cathepsin B (EC 3.4.22.1), cathepsin D (EC 3.4.23.5), aminopeptidase (EC 3.4.11.2), and a membrane-bound neutral metalloendopeptidase (EC 3.4.24.11) [10].
• Prolyl endopeptidase cleaves peptide bonds on the carboxyl side of proline residues within a peptide chain [11].

Biological context of Prep

• On the other hand, RC-Prep reduced the compound action potentials (cAPs) by 50% in 120 min [12].
• RC-Prep was the only agent to produce epinephrine-like contractions (vasoconstriction) in the rat carotid artery [13].
• The present investigation describes the comparative properties, particularly the substrate specificity of three kallikrein-like serine proteinases (I, II and III) purified from rat submandibular gland extract (Bedi, G.S., Prep. Biochem. 22,67-81, 1992) [14].
• Changes in prolyl endopeptidase during maturation of rat brain and hydrolysis of substance P by the purified enzyme [15].
• JTP-4819: a novel prolyl endopeptidase inhibitor with potential as a cognitive enhancer [1].

Anatomical context of Prep

• Caudal epididymal spermatozoa from rats with CRF but not from controls had been filtrated via Sperm Prep tubes to isolate the sperm fraction showing strong forward progressions [16].
• In this study, a 35% phosphoric acid gel (3M Scotchbond etchant), a nonrinse etchant (NRC), and two EDTA-containing conditioners (RC-Prep and File-Eze) were tested in vitro for blocking nerve conductance evoked in the rat sciatic nerve after local application [12].
• The enhancement of PE activity following STZ treatment was specific for pancreas tissue [2].
• In this work, we analyzed the effects of certain volume and/or osmotic changes in the activity of the soluble and membrane-bound prolyl endopeptidase in several brain areas, heart, lungs, kidney and adrenal and pituitary glands of the rat [17].
• Pharmacological studies of a novel prolyl endopeptidase inhibitor, JTP-4819, in rats with middle cerebral artery occlusion [18].

Associations of Prep with chemical compounds

• Prolyl endopeptidase (EC 3.4.21.26, PEP), a serine protease that hydrolyzes peptides at the carboxyl side of proline residues, is involved in the breakdown of several proline-containing neuropeptides and, thus, may contribute to the regulation of behavioral activities [19].
• The aldehyde was found to be a remarkably potent inhibitor of prolyl endopeptidase with a Ki of 14 nM [11].
• Their relative concentrations were ANG II >or= ANG-(1-7) > ANG III, and accumulation was modulated by quinapril, an inhibitor of angiotensin-converting enzyme (ACE), Z-proprolinal (ZPP), an inhibitor of prolyl endopeptidase (PEP), and parachloromercurylsulfonic acid (PCMS), an inhibitor of sulfhydryl protease [20].
• Rat serum catalyzed the degradation of 67.5 nmoles substrate/ml serum/h. The data indicate that TRH is degraded in rat serum predominantly by "thyroliberinase" and that prolyl endopeptidase and pyroglutamyl peptide hydrolase do not contribute significantly to this process [21].
• The identity of the enzymes catalyzing the degradation of thyrotropin releasing hormone (TRH) in rat serum was investigated by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase [21].

Other interactions of Prep

• Bestatin and puromycin were used to inhibit aminopeptidase activity, lisinopril for angiotensin-converting enzyme, phosphoramidon for neutral endopeptidase 24.11, and Z-Pro-prolinal for prolyl endopeptidase [22].
• Astrocytes are significantly enriched in post-proline cleaving dipeptidyl peptidase II, prolidase and aminopeptidase P activities; neurones and astrocytes contain prolyl endopeptidase [23].
• ZTTA, a prolyl endopeptidase inhibitor, potentiates the arginine-vasopressin-induced incorporation of [14C]leucine in rat amygdaloid and cortical slices [24].
• The activities of prolyl endopeptidase, pyroglutamyl peptidase I, puromycin sensitive aminopeptidase, and aminopeptidase N were assayed using beta-naphthylamine aminoacidic derivatives as substrates [25].
• In the hypothalamus both prolyl endopeptidase and dipeptidyl peptidase IV activities were concomitantly increased [26].

Analytical, diagnostic and therapeutic context of Prep

• Gel-filtration experiments of pancreatic extracts revealed that the total apparent activity of eluted PE in 3-day-old control rats was 2-fold higher than in the original extract [2].
• Cathepsin B and prolyl endopeptidase activity in rat peritoneal and alveolar macrophages. Stimulation of peritoneal macrophages by saline lavage [27].
• Selective prolyl endopeptidase inhibitors were elaborated by modification of the structure of SUAM-1221, by using a CoMFA study and protein crystallography [28].

References