Investigations of a catalytic antibody ligase and design and synthesis of phosphonate haptens for elicitation of antibodies capable of peptide bond formation / Barton W. Phillips.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Phillips, Barton W.

Contributor:

Hirschmann, Ralph, advisor.

Smith, Amos B., III, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Local Subjects:

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Physical Description:

xxiii, 334 pages : illustrations ; 29 cm

Production:

1998.

Summary:

This thesis describes the development and study of catalytic antibodies capable of peptide bond formation. The preparation of haptens for preparing such antibodies is described, as are the kinetics results obtained.

In Chapter 2, new methodologies for use in the preparation of phosphonate haptens are introduced. Use of a new chiral auxiliary {(-)-107 } was explored for use in the preparation of asymmetric alpha-aminophosphonates (-)-112. Development of a large scale Organic Synthesis preparative procedure around the use of auxiliary (-)- 107 is described. Furthermore, the identification of a new, activated phosphonylating species {(-)-156} is also discussed. This new species has proven highly effective in the preparation of hindered phosphonate esters.*

In Chapter 3, a survey of the activity of antibody 16G3 with a variety of substrates is described. The antibody proved an effective catalyst for the coupling of a variety of p-nitrophenyl esters; other esters were not accommodated by the antibody combining site. Antibody 16G3 also proved an efficient catalyst for the preparation of relatively unhindered tri- and tetrapeptides. Of particular interest is the ability of the antibody to catalyze formation of only the desired tripeptide (+)-199 in couplings involving the bis-nucleophile (-)-187. *

In Chapter 4, the design and synthesis of the second generation hapten (-)-243 is discussed. Twenty antibodies generated to hapten (-)-243 are currently undergoing testing. The description of azide substrates for testing of these antibodies is also described. *

*Please refer to dissertation for diagrams.

Notes:

Supervisors: Ralph Hirschmann; Amos B. Smith, III.

Thesis (Ph.D. in Chemistry) -- University of Pennsylvania, 1998.

Includes bibliographical references and index.

Local Notes:

University Microfilms order no.: 99-13510.

OCLC:

187478126