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dc.contributor.authorSwanson, Amanda Claire
dc.date.accessioned2020-05-14T15:36:43Z
dc.date.available2020-05-14T15:36:43Z
dc.date.issued2019
dc.identifier.otherW Thesis 1574
dc.identifier.urihttps://digitalrepository.wheatoncollege.edu/handle/11040/31261
dc.descriptionIncludes bibliographical references (leaves 50-54).
dc.description54 leaves : illustrations
dc.description.abstractHypertension is a leading risk factor for mortality that affects nearly a third of adult US residents, and it is primarily combatted through the use of angiotensin converting enzyme inhibitors (ACEIs). In addition to ACEIs currently approved as anti- hypertension drugs, there are a number of natural ACEIs that have not been studied, some of them more effective than others. This study sought to alter the structure of alanine- valine-phenylalanine (AVF), a natural, relatively ineffective ACEI, to create modified peptides that would hopefully act as more effective inhibitors. After a literature analysis, phenylalanine-valine-alanine (FVA) was determined to be more likely to act as an effective inhibitor, so four novel peptides were synthesized. One novel peptide was designed to contain unmodified phenylalanine while the other three contained one of the following para-substituted, N-protected, L-phenylalanine amino acids: L-Phenylalanine, N-benzoyl-4-methyl, L-Phenylalanine, N-benzoyl-4-methoxy-, L-Phenylalanine, N- benzoyl-4-fluoro-. In implementing these peptide modifications, first the respective modified phenylalanine amino acids were synthesized, then the FVA peptides were synthesized, with naturally occurring phenylalanine as well as the three modified phenylalanine amino acids. NMRs confirmed the identities of all products and HPLCdata confirmed the stereochemistry of the chiral amino acid intermediates.
dc.description.tableofcontents1 Introduction -- 1.1 Statement of the problem -- 1.2 Hypertension -- 1.2.1 Renin angiotensin system -- 1.2.2 Angiotensin converting enzyme inhibitors -- 1.2.3 Alanine-valine-phenylalanine -- 1.3 Modifications to AVF -- 1.4 Chirality -- 1.4.1 Chirality in drug synthesis -- 1.4.2 Chiral catalytic reduction -- 1.5 Peptide synthesis -- 1.6 In vitro assay -- 2 Results and discussion -- 2.1 Amino acids synthesis -- 2.2 Peptide synthesis -- 3 Experimental procedures -- 3.1 Synthesis of amino acids -- 3.2.1 Synthesis of oxazolones -- 3.2.2 Synthesis of enamide esters— 3.2.3 Synthesis of n-protected amino acid esters -- 3.2.4 Synthesis of n-protected amino acid -- 3.3 Peptide synthesis -- 3.3.1 Synthesis of FVA peptides -- 4 Conclusion -- 5.1 Conclusions and future research
dc.language.isoen_usen_US
dc.publisherWheaton College (MA)
dc.subjectUndergraduate research.
dc.subjectUndergraduate thesis.
dc.subject.lcshHypertension--United States.
dc.subject.lcshAngiotensin converting enzyme--Inhibitors.
dc.subject.lcshCaptopril.
dc.subject.lcshBlood circulation disorders--United States.
dc.titleStructural modification of a natural angiotensin converting enzyme inhibitor and the effect on activity.en_US
dc.typeThesisen


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