Browsing by Subject "peptidi"
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(2013)The aim of the literature review was to research barley proteins, metal-catalyzed oxidation and subjects related to it, like antioxidants and oxidation reactions in beer. In addition ACE inhibition was looked into. The object of the experimental part was to find out if the proteins of a barley-based industrial side product can be modified by metal-catalyzed oxidation or enzymatic hydrolysis, and how these treatments affect the different proteins in the sample material. In addition, the possible ACE inhibition activity of the reaction products was determined. The sample material was a protein-rich side-product of barley starch production. Two protein fractions were extracted from the material; an alcohol soluble fraction and a reduced fraction. The modification of the proteins in the sample fractions by oxidation and hydrolysis was determined with gel electrophoresis and size exclusion chromatography. The ACE inhibitory activity of the small peptides from these reactions was determined with UV-VIS spectroscopy. Three protein groups were identified from the sample material; polymeric B hordein, monomeric B hordein and C hordein. Contrary to expectations metal-catalyzed oxidation did not break down any of the proteins in the sample; instead it aggregated the proteins into bigger units. The enzyme treatment hydrolyzed the proteins effectively. Small peptides from the enzyme hydrolysis had an ACE inhibition IC50 of 246 µg/ml, which is similar to gluten hydrolysates IC50 of 29 µg/ml. IC50 is the inhibitor concentration where 50% of enzyme activity is inhibited. Instead of breaking down the subject proteins metal-catalyzed oxidation aggregated them, and thus it could not be used to make ACE inhibitory peptides. Enzyme hydrolysis was found to be a valid method of inhibitor peptide production. The peptides produced had an ACE inhibition capacity similar to previously known ACE inhibitory food hydrolysates.
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(2018)Formulation development for protein drugs should base on the knowledge of the mechanism of protein degradation. Excipients and formulation can be chosen to stabilize the protein and prevent decomposition. Stability testing is important to identify the likely degradation routes and provide information for formulation development and stability-indicating analytical method development. Gonadotropin-releasing hormone (GnRH) is a neuropeptide hormone that regulates the synthesis and release of gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FHS). Analogs of the endogenous GnRH have been developed to achieve more potent and longer-acting agonists or antagonists. GnRH agonists degrade in several pathways. The primary degradation routes are hydrolysis/backbone cleavage, oxidation, isomerization and aggregation. The stability of GnRH agonists in solid dosage forms has not been studied as excessively as in solutions. The objective of this study was to evaluate the stability of a GnRH agonist (API) at different storage conditions in powder form and in tablet formulations with maize starch or hydroxypropyl methylcellulose (HPMC). The samples were stored for three months at 5 °C (common refrigerator conditions) 25 °C/58 %RH (long-term conditions), and 40 °C/75 %RH (accelerated storage conditions). The samples were analyzed using high performance liquid chromatography. Additionally, the mechanical properties of the formulations and tablets were studied. The stability of API was confirmed in tablet dosage form, when maize starch or HPMC were used as excipients. No degradation products of API were found. As a pure powder API did not degrade either, but it did not stay physically stable at 40 °C/75 %RH. Stressed conditions could be used to find out degradation products in solid state that were not found in this study. Further, the formulations were not ideal, because neither of the studied excipient produced tablets with desirable properties.
Now showing items 1-2 of 2