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Monosaccharide-based beta turn mimetics for the somatostatin and neurokinin-1 receptors.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Monosaccharide-based beta turn mimetics for the somatostatin and neurokinin-1 receptors.
Author:	McVaugh, Cheryl T.
Description:	349 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-04, Section: B, page: 1735.
Notes:	Supervisors: Ralph Hirschmann; Amos B. Smith, III.
Contained By:	Dissertation Abstracts International64-04B.
Subject:	Chemistry, Organic.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3087434
ISBN:	0496352040

Monosaccharide-based beta turn mimetics for the somatostatin and neurokinin-1 receptors.
McVaugh, Cheryl T.

Monosaccharide-based beta turn mimetics for the somatostatin and neurokinin-1 receptors. [electronic resource] - 349 p.

Source: Dissertation Abstracts International, Volume: 64-04, Section: B, page: 1735.

Thesis (Ph.D.)--University of Pennsylvania, 2003.

*Please refer to dissertation for diagrams.

ISBN: 0496352040Subjects--Topical Terms:

193634
Chemistry, Organic.

Monosaccharide-based beta turn mimetics for the somatostatin and neurokinin-1 receptors.
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245 1 0 $a Monosaccharide-based beta turn mimetics for the somatostatin and neurokinin-1 receptors. $h [electronic resource]
300 $a 349 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-04, Section: B, page: 1735.
500 $a Supervisors: Ralph Hirschmann; Amos B. Smith, III.
502 $a Thesis (Ph.D.)--University of Pennsylvania, 2003.
520 # $a *Please refer to dissertation for diagrams.
520 # $a In Chapter 1, the application of mono saccharide-based peptidomimetics at the human somatostatin subtype-4 (hSST4) receptor is discussed. Incorporation of heterocyclic substituents, such as pyridin-3-ylmethyl, pyrazin-2-ylmethyl and 2-fluoropyridin-3-ylmethyl (typified by (+)-1--2), at the C4 position of the glucose scaffold afforded an unexpected affinity enhancement. Evidence suggests that a hydrogen bond between the substituent and the hSST4 receptor is responsible for this affinity enhancement. Additionally, incorporation of an imidazole substituent at the C2 position afforded (-)-1--28, a 53 nM hSST4 ligand. Preparation of (-)-1--29 to explore this affinity-enhancement revealed that imidazole by itself is not enough to enhance affinity in this series, but the presence of pyridin-3-ylmethyl is required. This resulted is explained by conformational analysis wherein the exocyclic C-O bond is eclipsed.*
520 # $a In Chapter 2, the affinity of (+)-0--1 for the neurokinin-1 receptor (hNK-1) is attempted to be explained through structural correlation with other classes of NK-1 receptor ligands. In Chapter 3 describes how optimization of the affinity of (+)-0--1 at the NK-1 receptor was accomplished by placing the side chains at different contiguous positions on the glucose scaffold; elucidation of the SAR of (-)-3--4 led to the discovery of 8 nM hNK-1 receptor ligand (-)-3--12. Finally, the radial symmetry inherent to the glucose scaffold is postulated to be a major contributing factor for the established usefulness of former in lead discovery.*
520 # $a This dissertation describes the design and synthesis of mono saccharide-based peptidomimetics for the somatostatin and neurokinin-1 receptors. The introductory chapter gives a brief overview of the use of carbohydrates as peptidomimetic scaffolds, with examples from the Hirschmann-Smith laboratories, as well as the laboratories of others.
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790 1 0 $a Smith, Amos B., III, $e advisor
791 $a Ph.D.
792 $a 2003
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