Thesis (Ph. D.)--Ohio State University, 2007. / Full text release at OhioLINK's ETD Center delayed at author's request

Thesis (Ph. D.)--University of Delaware, 2007. / Principal faculty advisor: Darrin J. Pochan, Dept. of Materials Science & Engineering. Includes bibliographical references.

Lic-avh. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 3 uppsatser.

Thesis (doctoral)--Lund University, 1997.

Thesis (doctoral)--Karolinska Institutet, Stockholm, 1989. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Karolinska Institutet, Stockholm, 1983. / Extra t.p. with thesis statement inserted. Includes the author's four published papers. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (doctoral)--Karolinska Institutet, Stockholm, 1983. / Extra t.p. with thesis statement inserted. Includes the author's four published papers. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (doctoral)--Lund University, 1997.

The objective of this work was to produce bioactive peptides from the enzymatic hydrolysis of chicken skin proteins that could be used to treat hypertension, oxidative stress and associated health conditions using a metabolomics approach. Enzymatic hydrolysis of chicken thigh and breast muscle skin proteins was carried out using alcalase or a combination of pepsin/pancreatin (PP) at 1–4% enzyme concentrations. Chicken skin protein hydrolysates (CSPH) were each fractionated by membrane ultrafiltration into different molecular weight peptides (<1, 1–3, 3–5 and 5–10 kDa). Investigation of their in vitro antihypertensive and antioxidant activities showed that alcalase hydrolysates had significantly (p < 0.05) higher ACE-inhibitory activity compared to PP hydrolysates. ACE inhibition was inversely related to size of ultrafiltration membrane peptides. Renin-inhibitory activity varied from 15–36%, and was dependent on the type of protease; PP hydrolysates showed significantly (p < 0.05) higher inhibition than alcalase hydrolysates. CSPHs also significantly (p < 0.05) scavenged antioxidant radicals, increasing with enzyme concentration but decreased as peptide size increased. Kinetics studies revealed that peptide-dependent enzyme inhibition pattern was mostly of the mixed-type for both ACE and renin. Short-term (24 hr) oral administration of 100 mg peptides/kg body weight to spontaneously hypertensive rats (SHRs) led to maximum systolic blood pressure (SBP) reduction of –32.67 and –31.33 mmHg after 6 h for chicken thigh skin hydrolysate and chicken breast skin hydrolysate, respectively. During a 6-week feeding trial, CSPH at 1.0 and 0.5% feed substitutions had significant (p<0.05) antihypertensive effects in SHRs (-36 and -31 SBP reductions, respectively). SBP reduction was directly related to lower plasma ACE but not renin activity. Plasma total antioxidant capacity of the rats was also high. Metabolomics analysis revealed several metabolites with significant changes (≥ 2-fold changes, p < 0.05) in urine and plasma of SHRs fed CSPH, such as Symmetric Dimethylarginine (SDMA), N2-acetyl-L-ornithine, buthionine sulfoximine, uric acid, Vitamin E succinate, L-isoleucine and phospholipids which may be considered important biomarkers/pathways for hypertension and oxidative stress. We conclude that CSPHs may be used as ingredients to formulate functional foods and nutraceuticals for the management of oxidative stress and hypertension-related diseases. / October 2015

N-carboxy-α-amino acid anhydrides (NCAs) are amino acid derivatives discovered by Leuch in 1906. Ever since, they have found invaluable use in the preparation of peptide drugs and polypeptides. NCAs are generally synthesised using phosgene; however, due to the hazardous nature of this chemical, safer method of synthesis using protected amino acids in the presence of activating reagents such as P2O4, T3P, HBTU and BOP-Cl were investigated, where a protonated oxazolone intermediate is dealkylated to generate the corresponding amino acid NCA. After the successful synthesis of a variety of NCAs, starting from Boc-protected amino acids and using T3P, we attempted to work out a new method of sequential peptide synthesis using NCAs in a controlled way. The challenge involved in the use of NCAs in the synthesis of peptides is to prevent decarboxylation of the intermediate products, which lead to the generation of unwanted peptide oligomers. An elegant way to prevent the decarboxylation was studied in this work, which consists of the stabilisation of the carbamate intermediates using an appropriate receptor. We prepared several carbamate receptors and tested them in model reactions using amines and NCAs under various conditions. Despites partial success in limiting the amount of oligomerisation, we were never able to prevent it completely, and could not established conditions to prepare peptides in good purity.