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 #
4R01CA169140-04
Application #
9039005
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
2016-04-01
Budget End
2017-03-31
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Type
University-Wide
DUNS #
153926712
City
Amherst
State
MA
Country
United States
Zip Code
Gao, Jingjing; Zhao, Bo; Wang, Meizhe et al. (2018) Supramolecular Assemblies for Transporting Proteins Across an Immiscible Solvent Interface. J Am Chem Soc 140:2421-2425
Zhao, Bo; Serrano, Mahalia A C; Gao, Jingjing et al. (2018) Self-assembly of random co-polymers for selective binding and detection of peptides. Polym Chem 9:1066-1071
Serrano, Mahalia A C; Zhao, Bo; He, Huan et al. (2018) Molecular Features Influencing the Release of Peptides from Amphiphilic Polymeric Reverse Micelles. Langmuir 34:4595-4602
Zhao, Bo; Serrano, Mahalia A C; Wang, Meizhe et al. (2018) Improved mass spectrometric detection of acidic peptides by variations in the functional group pKa values of reverse micelle extraction agents. Analyst 143:1434-1443
Liu, Bin; Thayumanavan, S (2017) Importance of Evaluating Dynamic Encapsulation Stability of Amphiphilic Assemblies in Serum. Biomacromolecules 18:4163-4170
Raghupathi, Kishore; Thayumanavan, Sankaran (2017) Nano-Armoring of Enzymes: Rational Design of Polymer-Wrapped Enzymes. Methods Enzymol 590:381-411
Liu, Bin; Thayumanavan, S (2017) Substituent Effects on the pH Sensitivity of Acetals and Ketals and Their Correlation with Encapsulation Stability in Polymeric Nanogels. J Am Chem Soc 139:2306-2317
Wang, Meizhe; Zhao, Bo; Gao, Jingjing et al. (2017) Altering the Peptide Binding Selectivity of Polymeric Reverse Micelle Assemblies via Metal Ion Loading. Langmuir 33:14004-14010
Serrano, Mahalia A C; He, Huan; Zhao, Bo et al. (2016) Polymer-mediated ternary supramolecular interactions for sensitive detection of peptides. Analyst 142:118-122
Ventura, Judy; Eron, Scott J; González-Toro, Daniella C et al. (2015) Reactive Self-Assembly of Polymers and Proteins to Reversibly Silence a Killer Protein. Biomacromolecules 16:3161-71

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