Towards the development of cryptophane biosensors for cancer detection/ Garry K Seward.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Seward, Garry K.

Contributor:

Dmochowski, Ivan J., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Local Subjects:

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Physical Description:

ix, 169 pages : illustrations (some color) ; 29 cm

Production:

2010.

Summary:

This dissertation describes progress in the development of cryptophanes for early cancer detection by magnetic resonance. Propargyl substituted cryptophanes were functionalized with peptides through [3+2] cycloadditions. A peptide substrate for the cancer related enzyme matrix metalloproteinase-7 was attached to cryptophane and the kinetics of enzyme cleavage were monitored. 129Xe NMR spectra were collected for the compound before and after cleavage to examine the effect of enzyme activity on chemical shift. Similarly two cell penetratin peptides were attached to cryptophane by "click chemistry" reactions. These uptake of the conjugates was monitored by fluorescence microscopy. Viability assays revealed the effects of cryptophane delivery on cell growth. Lastly, two peptide ligands for the cell surface receptor alphavbeta 3 integrin were attached to cryptophane. Using fluorescence microscopy, cellular uptake through the receptor mediated pathway was investigated. Binding studies performed with one of the conjugates revealed that cryptophane only slightly diminished binding to protein receptors.

Notes:

Adviser: Ivan J. Dmochowski.

Thesis (Ph.D. in Chemistry) -- University of Pennsylvania, 2010.

Includes bibliographical references.