Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many biologically important peptide sequences contain proline. It confers unique conformational constraints on the peptide chain in that the side-chain is cyclized back onto the backbone amide position. Inside an alpha-helix the possibility of making hydrogen bonds to the preceding turn is lost and a kink will be introduced. The conformational restrictions imposed by proline motifs in a peptide chain appear to imply important structural or biological functions as can be deduced from their often remarkably high degree of conservation as found in many proteins and peptides, especially cytokines, growth factors, G-protein-coupled receptors, V3 loops of the HIV envelope glycoprotein gp 120, and neuro- and vasoactive peptides. Only a limited number of peptidases are known to be able to hydrolyze proline adjacent bonds. Their activity is influenced by the isomeric state (cis-trans) as well as the position of proline in the peptide chain. The three proline specific metallo-peptidases (aminopeptidase P, carboxypeptidase P and prolidase) are activated by Mn2+, whereas the three serine type peptidases cleaving a post proline bond (prolyl oligopeptidase, dipeptidyl peptidase IV, and prolylcarboxypeptidase) share the sequential order of the catalytic Ser-Asp-His triade, which differentiates them from the chymotrypsin (His-Asp-Ser) and subtilisin (Asp-His-Ser) families. An endo or C terminal Pro-Pro bond and an endo pre-Pro peptide bond possess a high degree of resistance to any mammalian proteolytic enzyme.
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PMID:Proline motifs in peptides and their biological processing. 760 38

A novel mucoadhesive drug carrier system has been generated which protects a model polypeptide antigen from degradation by the most abundant intestinal proteases. The enzyme inhibitors antipain, chymostatin and elastatinal, respectively, were covalently attached to the mucoadhesive polymer sodium carboxymethylcellulose (NaCMC) and the inhibitory efficacy of the resulting polymer-inhibitor conjugates was evaluated in vitro. When these inhibitor conjugates were combined with the thiolated polymer polycarbophil-cysteine (PCP-Cys), 95.8 +/- 3.8% (mean +/- SD, n = 3) of the incorporated model antigen ovalbumin (OVA) was protected from enzymatic degradation within 90 min incubation in the presence of an artificial intestinal fluid containing the pancreatic serine proteases trypsin, chymotrypsin and elastase. Replacing the CMC-inhibitor conjugates in the dosage form by unmodified CMC significantly reduced the protective effect to 78.8 +/- 4.7% (mean +/- SD, n = 3), whereas incorporation of the model antigen in a CMC dosage form omitting PCP-Cys protected 72.5 +/- 3.2% (mean +/- SD, n = 3) of OVA from degradation within a 90 min incubation period. Further, the incorporation of PCP-Cys resulted in higher cohesiveness within the dosage form and controlled drug release of the antigen for a time period of more than 9 h. Results suggest that a delivery system combining thiolated polymer and polymer-inhibitor conjugates improves the metabolic stability of the model polypeptide antigen and may therefore be a useful tool for oral protein vaccination.
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PMID:Design and in vitro evaluation of a mucoadhesive oral delivery system for a model polypeptide antigen. 1159 93

Cystine-knot microproteins exhibit several properties that make them highly interesting as scaffolds for oral peptide drug delivery. It was therefore the aim of the study to evaluate the novel clinically relevant cystine-knot microprotein McoEeTI regarding its potential for oral delivery. Additionally, based on the gained results, important features of McoEeTI were improved. Enzymatic degradation was caused by chymotrypsin, trypsin and porcine small intestinal juice whereas McoEeTI was stable towards elastase, membrane bound proteases, pepsin and porcine gastric juice. Only minor McoEeTI degradation was observed during a 24h incubation period in rat plasma. In the presence of various physiological ions about 50% of McoEeTI formed di- and/or trimers. P(app) value of McoEeTI was determined to be (7.4+/-0.4)x10(-6)cm/s. Sodium caprate and polycarbophil-cysteine (PCP-Cys) had no beneficial effect on McoEeTI permeation, whereas the utilization of a chitosan-thiobutylamidine (Chito-TBA) system improved McoEeTI permeation 3-fold. Enzymatic stability could be strongly improved by the utilization of Bowman-Birk-Inhibitor (BBI) as well as PCP-Cys. In conclusion, this study indicates that McoEeTI represents a promising candidate as a novel scaffold for oral peptide drug delivery.
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PMID:Evaluation and improvement of the properties of the novel cystine-knot microprotein McoEeTI for oral administration. 1707 Jun 61