Persistent Link:
http://hdl.handle.net/10150/187626
Title:
SYNTHESIS AND CONFORMATIONAL STUDIES OF OXYTOCIN ANALOGS.
Author:
ROCKWAY, TODD WARREN.
Issue Date:
1983
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The preparation of 11 new oxytocin analogs is described. The synthesis of the protected peptides were performed using solid phase peptides synthetic methodology. The protected peptides were deprotected and cyclized using sodium in liquid ammonia followed by aqueous potassium ferricyanide treatment. The purification of each peptide was accomplished using partition chromatography followed by gel filtration. Final purity was checked using high-performance liquid chromatography. Several amino-acid derivatives were prepared and incorporated as racemates into the synthetic peptides. The synthetic diastereomeric peptides were separated and purified by high pressure liquid chromatography using aqueous trifluoroacetic acid:acetonitrile mixtures. The oxytocin analogs prepared in this dissertation were divided into 2 classes: oxytocin agonists and oxytocin antagonists. The oxytocin agonist analogs prepared are [2-cycloleucine]oxytocin and [8-cycloleucine]oxytocin. The oxytocin antagonists described in this dissertation are [Pen¹,Cle²]oxytocin, [Pen¹,Cle⁸]oxytocin, [Pen¹,L-TyrMe²,Thr⁴,Orn⁸]oxytocin, [Pen¹,L-TyrEt²,Thr⁴,Orn⁸]oxytocin, [Pen¹,D-TyrEt²,Thr⁴,Orn⁸]oxytocin, [Pen¹,L-PheMe²,Thr⁴,Orn⁸]oxytocin, [Pen¹,L-PheEt²,Thr⁴,Orn⁸]oxytocin, [Pen¹,D-PheMe²,Thr⁴,Orn⁸]oxytocin and [Pen¹,D-PheEt²,Thr⁴,Orn⁸]oxytocin. A conformational study of the synthetic peptides was also undertaken in order to determine possible solution conformations for the various peptides. Two biophysical methods were used in the conformational study of these peptides; they include nuclear magnetic resonance spectroscopy (H-1 and C-13) and circular dichroism spectroscopy. Two somewhat different solution conformations were discovered for peptides containing all L-amino acids and for peptides containing a D-amino acid residue in position 2. A possible correlation between biological potency and observed solution conformation is suggested; the proposed models may aid in the design of more potent peptide inhibitor analogs.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Peptide hormones.; Peptides -- Synthesis.; Oxytocin.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Chemistry; Graduate College
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleSYNTHESIS AND CONFORMATIONAL STUDIES OF OXYTOCIN ANALOGS.en_US
dc.creatorROCKWAY, TODD WARREN.en_US
dc.contributor.authorROCKWAY, TODD WARREN.en_US
dc.date.issued1983en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe preparation of 11 new oxytocin analogs is described. The synthesis of the protected peptides were performed using solid phase peptides synthetic methodology. The protected peptides were deprotected and cyclized using sodium in liquid ammonia followed by aqueous potassium ferricyanide treatment. The purification of each peptide was accomplished using partition chromatography followed by gel filtration. Final purity was checked using high-performance liquid chromatography. Several amino-acid derivatives were prepared and incorporated as racemates into the synthetic peptides. The synthetic diastereomeric peptides were separated and purified by high pressure liquid chromatography using aqueous trifluoroacetic acid:acetonitrile mixtures. The oxytocin analogs prepared in this dissertation were divided into 2 classes: oxytocin agonists and oxytocin antagonists. The oxytocin agonist analogs prepared are [2-cycloleucine]oxytocin and [8-cycloleucine]oxytocin. The oxytocin antagonists described in this dissertation are [Pen¹,Cle²]oxytocin, [Pen¹,Cle⁸]oxytocin, [Pen¹,L-TyrMe²,Thr⁴,Orn⁸]oxytocin, [Pen¹,L-TyrEt²,Thr⁴,Orn⁸]oxytocin, [Pen¹,D-TyrEt²,Thr⁴,Orn⁸]oxytocin, [Pen¹,L-PheMe²,Thr⁴,Orn⁸]oxytocin, [Pen¹,L-PheEt²,Thr⁴,Orn⁸]oxytocin, [Pen¹,D-PheMe²,Thr⁴,Orn⁸]oxytocin and [Pen¹,D-PheEt²,Thr⁴,Orn⁸]oxytocin. A conformational study of the synthetic peptides was also undertaken in order to determine possible solution conformations for the various peptides. Two biophysical methods were used in the conformational study of these peptides; they include nuclear magnetic resonance spectroscopy (H-1 and C-13) and circular dichroism spectroscopy. Two somewhat different solution conformations were discovered for peptides containing all L-amino acids and for peptides containing a D-amino acid residue in position 2. A possible correlation between biological potency and observed solution conformation is suggested; the proposed models may aid in the design of more potent peptide inhibitor analogs.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectPeptide hormones.en_US
dc.subjectPeptides -- Synthesis.en_US
dc.subjectOxytocin.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.committeememberGlass, Richard S.en_US
dc.contributor.committeememberMartin, Arnold R.en_US
dc.contributor.committeememberSteelink, Corneliusen_US
dc.identifier.proquest8405508en_US
dc.identifier.oclc690667686en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.