Recognizing specific molecules and reporting their presence in a complex mixture is a significant challenge, and this proposal outlines a new supramolecular approach to address this problem. There has been a great interest in detecting biomarkers in small concentrations in physiological fluids, such as serum, because of the implications in early detection of diseases. In this proposal, we focus on peptide- and protein-based biomarkers, the detection of which is of interest in the early diagnosis of cancer - a criticl factor in effective cancer treatment. The preliminary results are very encouraging and it is essential that we further develop this approach for real-life systems by understanding the factors that underlie the binding and detection events. The proposed research is focused on this purpose. The key elements of our approach are that: (i) our polymer assemblies are kinetically trapped in the assembled solvent and maintain their supramolecular fidelity under a broad range of conditions;(ii) these assemblies bind to a selective set of peptides to move them from the aqueous to the organic phase;(iii) our polymers provide signal enhancements that greatly enhance the sensitivity of detection;and (iv) the proposed experimental protocols allow for concurrent detection of several biomarkers sensitively. These promising features will be rigorously tested for detecting cancer biomarkers in complex physiological fluids, serum and breast milk. Note that we focus on well-established cancer biomarkers to allow us to focus squarely on testing the versatility of new approach.

Public Health Relevance

This project describes novel strategies for supramolecular assemblies formed from facially amphiphilic macromolecules to detect peptides and proteins with very high sensitivity in physiological fluids. The project specifically focuses on detecting cancer biomarkers with very high sensitivity in complex mixtures.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA169140-02
Application #
8634074
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Kagan, Jacob
Project Start
2013-04-01
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
2
Fiscal Year
2014
Total Cost
$310,813
Indirect Cost
$109,538
Name
University of Massachusetts Amherst
Department
None
Type
Other Domestic Higher Education
DUNS #
153926712
City
Amherst
State
MA
Country
United States
Zip Code
01003
Raghupathi, Krishna R; Guo, Jing; Munkhbat, Oyuntuya et al. (2014) Supramolecular disassembly of facially amphiphilic dendrimer assemblies in response to physical, chemical, and biological stimuli. Acc Chem Res 47:2200-11
Gonzalez-Toro, Daniella C; Thayumanavan, S (2013) Advances in Polymer and Polymeric Nanostructures for Protein Conjugation. Eur Polym J 49:2906-2918
Wang, Feng; Gomez-Escudero, Andrea; Ramireddy, Rajasekhar R et al. (2013) Electrostatic control of peptide side-chain reactivity using amphiphilic homopolymer-based supramolecular assemblies. J Am Chem Soc 135:14179-88