PART I. DESIGN AND SYNTHESIS OF BICYCLIC INTERNAL BETA-TURN MIMETICS AND THEIR INCORPORATION INTO BIOLOGICALLY ACTIVE LIGANDS; PART II. SYNTHESIS OF CYCLIC PEPTIDES BY RING

Persistent Link:
http://hdl.handle.net/10150/194081
Title:
PART I. DESIGN AND SYNTHESIS OF BICYCLIC INTERNAL BETA-TURN MIMETICS AND THEIR INCORPORATION INTO BIOLOGICALLY ACTIVE LIGANDS; PART II. SYNTHESIS OF CYCLIC PEPTIDES BY RING
Author:
Min, Byoung Joon
Issue Date:
2010
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:
beta-Turns in many biologically active peptides are important secondary structural elements which are critical for their biological activities. Hence, it is not surprising that beta-turn based pharmacophore design including beta-turn mimetics has become a central topic in medicinal chemistry in addition to alpha-helix or helical peptides. One of the advantages of such beta-turn mimetics is that they can better control torsion angles of the backbone of peptides and to some degree dihedral angles chi (X). These beta-turn mimicking scaffolds are designed to have a higher avidity for the acceptor by overcoming what otherwise is the inherent entropic cost paid for beta-turn formation upon binding to the acceptor. Among different synthetic strategies to bicyclic structures as beta-turn mimetics, consecutive formation of bicyclic structures using tandem acid-catalyzed N-acyliminium ion cyclization is attractive since this methodology was well established in the synthesis of natural product alkaloids. 1,3,6,8-Substituted tetrahydro-2H-pyrazino[1,2-a]pyrimidine-4,7-diones were designed and synthesized as internal beta-turn mimetics through an acid-catalyzed tandem acyliminium ion cyclization. Its development and synthesis are decribed in Chapter 2 to Chapter 4. Its application toward the development and synthesis of a small molecule ligand for melanocortin receptors is described in Chapter 5. In addition, the development of peptidomimetics for opioid receptors is explained in Chapter 6. On the other hand, a dicarba analogue having opioid receptor agonist, and dicarba analogues for MCRs were synthesized through solid phase synthesis including a ring closing metathesis reaction using Grubbs' catalyst (I) in Chapter 8.
Type:
text; Electronic Dissertation
Keywords:
beta-turn mimectics; melarnocortin receptor ligands; N-acylimminium ion cyclization; neurokinin receptor ligands; opioid ligands; ring closing metathesis
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Chemistry; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Hruby, Victor J.
Committee Chair:
Hruby, Victor J.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titlePART I. DESIGN AND SYNTHESIS OF BICYCLIC INTERNAL BETA-TURN MIMETICS AND THEIR INCORPORATION INTO BIOLOGICALLY ACTIVE LIGANDS; PART II. SYNTHESIS OF CYCLIC PEPTIDES BY RINGen_US
dc.creatorMin, Byoung Joonen_US
dc.contributor.authorMin, Byoung Joonen_US
dc.date.issued2010en_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.abstractbeta-Turns in many biologically active peptides are important secondary structural elements which are critical for their biological activities. Hence, it is not surprising that beta-turn based pharmacophore design including beta-turn mimetics has become a central topic in medicinal chemistry in addition to alpha-helix or helical peptides. One of the advantages of such beta-turn mimetics is that they can better control torsion angles of the backbone of peptides and to some degree dihedral angles chi (X). These beta-turn mimicking scaffolds are designed to have a higher avidity for the acceptor by overcoming what otherwise is the inherent entropic cost paid for beta-turn formation upon binding to the acceptor. Among different synthetic strategies to bicyclic structures as beta-turn mimetics, consecutive formation of bicyclic structures using tandem acid-catalyzed N-acyliminium ion cyclization is attractive since this methodology was well established in the synthesis of natural product alkaloids. 1,3,6,8-Substituted tetrahydro-2H-pyrazino[1,2-a]pyrimidine-4,7-diones were designed and synthesized as internal beta-turn mimetics through an acid-catalyzed tandem acyliminium ion cyclization. Its development and synthesis are decribed in Chapter 2 to Chapter 4. Its application toward the development and synthesis of a small molecule ligand for melanocortin receptors is described in Chapter 5. In addition, the development of peptidomimetics for opioid receptors is explained in Chapter 6. On the other hand, a dicarba analogue having opioid receptor agonist, and dicarba analogues for MCRs were synthesized through solid phase synthesis including a ring closing metathesis reaction using Grubbs' catalyst (I) in Chapter 8.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectbeta-turn mimecticsen_US
dc.subjectmelarnocortin receptor ligandsen_US
dc.subjectN-acylimminium ion cyclizationen_US
dc.subjectneurokinin receptor ligandsen_US
dc.subjectopioid ligandsen_US
dc.subjectring closing metathesisen_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.advisorHruby, Victor J.en_US
dc.contributor.chairHruby, Victor J.en_US
dc.contributor.committeememberWysocki, Vicki H.en_US
dc.contributor.committeememberZheng, Zhipingen_US
dc.contributor.committeememberPyun, Jeffreyen_US
dc.contributor.committeememberChristie, Hamish S.en_US
dc.identifier.proquest10996en_US
dc.identifier.oclc659754929en_US
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