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Professor Nag's lab develops unique peptide or peptidomimetic macrocycles using robust chemical reactions and Solid Phase Peptide Synthesis. Macrocycles, with molecular weights of approximately 1000, bridge the gap between small molecules and proteins, in terms of size and composition. Chemical synthesis of macrocycles allows one to incorporate unique properties such as thermal and protease stability and inclusion of small molecules. Harnessing the power of molecular recognition in macrocycles, we currently are working on different aspects of biological chemistry and catalysis.
Currently her group is focused on the following themes:
1. Macrocyclic peptides as potential Cancer Therapeutics Intracellular regulatory proteins involved in cell signaling frequently interact with each other through large surface areas, a phenomenon termed as Protein Protein Interactions (PPi), and aberrant PPI can lead to diseases like cancer. Peptide macrocycles, with their extended structures, can occupy efficiently the large protein surfaces involved in PPI, and therefore can inhibit prevent aberrant intracellular PPI. The Nag lab is developing a technology to synthesize and screen novel peptide macrocycles which can penetrate the cell membranes and selective target the protein interaction surfaces.
2. Designing biomimetic catalytic centers
Complexes of transition metals like copper and nickel with peptide and peptidomimetic macrocycles can be visualized as miniature versions of photosynthetic proteins such as Photosystem I and Photosystem II. While the proteins are excellent catalysts, they degrade rapidly outside the cellular environment. The Nag Lab is trying to optimize the motifs of known linear peptides, as complexes with metals, for efficiency as water oxidation catalysts. Future work will involve development of unique macrocycle –metal or organic ligand - metal catalytic centers as catalysts for homogeneous and heterogeneous water oxidation and carbon dioxide reactions.
3. Developing biological small molecule sensors
Building on our previous research on selective recognition of phospho-serine and phosphorylated proteins, we plan to develop macrocyclic reagents for recognition of phosphate containing biological small molecules. Selective recognition will involve not only the phosphate moiety sensing but also unique sensing of other parts of the small molecule. Unique elements in the macrocycles will enable phosphate recognition while amino acid components of the macrocycle will allow selective recognition of the small molecule.
Degrees
- Ph.D. in Chemistry, California Institute of Technology, 2013
- M.S. in Chemistry, Indian Institute of Technology, 2006
- B.S. in Chemistry, Presidency College, University of Calcutta, 2004
Affiliated Department(s)
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Scholarly and Creative Works
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Water oxidation catalysis properties of copper complex with N-methylated gly4 peptide in an oxidative environment in buffer solution
Published in Chem Comm
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2024
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Peptide and Peptide Mimicking Tools: Synthesis and Methods
Chapter: Tetrazine cyclized library for One-Bead-One-Compound library: synthesis and sequencingPublished by Elsevier
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2024
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A copper-selective sensor and its inhibition of copper-amyloid beta aggregation
Published in Biosensors
Spring
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2024
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Development of immobilized copper-ligand complex for click chemistry of biomolecules
Published in Molecules
Spring
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2024
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Engineering of cyclic peptides for cell penetration
Published in Acs Chemical Biology
Spring
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2024
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Published in Chembiochem
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2023
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A library of copper-peptide/peptidomimetic complexes to explore the effect of ligand framework modification on electrocatalytic water oxidationÂ
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2023
ChemRxiv
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Published in Communications Chemistry
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2023
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Il-17f-specific capture agents, compositions, and methods of using and making
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2021
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Cyclic peptide binder against oncogenic K-Ras
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2021
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Cyclic peptides as protein targeting agents
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2021
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Peptide Macrocycles Methods and Protocols
Chapter: Binding characterization of cyclic peptide ligands to target proteins and chemical epitopes using ELISA and Fluorescence Polarization assaysPublished by Springer
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2021
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Fluorescent Sensors of Phosphate Containing Biomolecules
Published in Israel Journal of Chemistry
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2021
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Vol. 61
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Issue #3-4
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Copper ligand clusters dictate size of cyclized peptide formed during alkyne azide cycloaddition on solid support
Published in RSC Adv.
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2021
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Vol. 11
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Chemical Epitope Targeting: Review ofa Novel Screening Technology
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2019
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Akt-specific capture agents, compositions, and methods of using and making
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2019
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Biological applications of amide and amino acid containing synthetic macrocycles
Published in Supramolecular Chemistry
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2019
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Vol. 31
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Issue #8
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Corrigendum: Epitope Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent In-Cell Inhibitor of Botulinum Neurotoxin
Published in Angewandte Chemie International Edition
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2018
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Vol. 57
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Issue #6
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Investigation of on-resin reactions for cyclization efficiency to control monomer/dimer ratios for comprehensive macrocyclic peptide libraries
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY●
2018
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Vol. 256
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Cyclic peptide binder against oncogenic K-Ras
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2018
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Il-17f and il-17a-specific capture agents, compositions, and methods of using and making
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2018
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Chemical Epitope Targeting: Review of a Novel Screening Technology
Published in Journal of Medicinal Chemistry and Drug Design
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2018
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Vol. 1
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Issue #2
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Circle Akt in: Epitope catalyzed assembly of macrocyclic therapeutics against phosphorylated Akt
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2016
American Association for Cancer Research
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Rapid discovery of peptidomimetics as antibody alternatives via epitope-targeted screening
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2016
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Circle Akt In: Macrocycles against phosphorylated Akt
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2016
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Detection of a Geographically Diverse Malarial Biomarker via Multi-Epitope Targeted Screening
Published in Biophysical Journal
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2016
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Vol. 110
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Issue #3
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Degradation of Akt using protein-catalyzed capture agents
Published in Journal of Peptide Science
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2016
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Vol. 22
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Issue #4
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Akt-specific capture agents, compositions, and methods of using and making
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2016
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A general synthetic approach for designing epitope targeted macrocyclic peptide ligands
Published in Angewandte Chemie International Edition
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2015
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Vol. 54
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Issue #45
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Phosphorylated akt-specific capture agents, compositions, and methods of using and making
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2015
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Epitope Targeting of Tertiary Protein Structure Enables Target-Guided Synthesis of a Potent In-Cell Inhibitor of Botulinum Neurotoxin
Published in Angewandte Chemie
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2015
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Vol. 127
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Issue #24
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A protein-targeting strategy used to develop a selective inhibitor of the E17K point mutation in the PH domain of Akt1
Published in Nature chemistry
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2015
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Vol. 7
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Issue #5
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Cyclic peptides as protein targeting agents
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2015
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Capture agents and related compositions, methods and systems
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2015
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Developing peptide based capture agents for diagnostics and therapeutics
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2013
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In situ click chemistry: from small molecule discovery to synthetic antibodies
Published in Integrative Biology
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2013
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Vol. 5
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Issue #1
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A Chemical Epitope-Targeting Strategy for Protein Capture Agents: The Serine 474 Epitope of the Kinase Akt2
Published in Angewandte Chemie
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2013
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Vol. 125
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Issue #52
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Iterative in situ click chemistry assembles a branched capture agent and allosteric inhibitor for Akt1
Published in Journal of the American Chemical Society
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2011
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Vol. 133
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Issue #45
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Iterative in situ click chemistry creates antibody-like protein-capture agents
Published in Angewandte Chemie International Edition
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2009
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Vol. 48
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Issue #27
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Effects of ion concentration on the hydrogen bonded structure of water in the vicinity of ions in aqueous NaCl solutions
Published in Journal of Chemical Sciences
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2008
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Vol. 120
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Issue #1
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Awards & Grants
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CAREER: Macrocyclic Peptidomimetic Scaffolds for Sensing of Phosphate-containing Metabolites
National Science Foundation
Oct. 1, 2022 - Sep. 30, 2027
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NSF LEAPS-MPS: Macrocyclic Peptidomimetic Scaffolds for Sensing of Phosphate-containing Metabolites
National Science Foundation
Sep. 30, 2022 - Sep. 30, 2024
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Development of a novel proximity-catalyzed Chemical Epitope Targeting technology for isolating macrocyclic peptide inhibitors of KRas (G12V)- Sos interaction
National Institute of Health
Sep. 1, 2020 - Aug. 31, 2024
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Development of Cysteine-quinone reaction aided Chemical Epitope Targeting technology for isolating peptide inhibitors of KRAS(G12C)-SOS interaction
Cottrell Scholar Award, Research Corporation for Science Advancement
Aug. 1, 2021 - Jul. 30, 2024
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Hydrocarbon metathesis on peptide-small molecule scaffold
American Chemical Society Petroleum Research Fund
Sep. 1, 2020 - Aug. 31, 2022
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Environment-friendly mononuclear and binuclear copper-peptide complexes as water oxidation catalysts
American Association of University Women
Jul. 15, 2020 - Jul. 15, 2021
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Environment-friendly mononuclear and binuclear copper-peptide complexes as water oxidation catalysts
American Association of University Women
Oct. 1, 2018 - Oct. 1, 2019
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CAREER:Macrocyclic Peptidomimetic Scaffolds for Sensing of Phosphate-containing Metabolites
National Science Foundation
Oct. 1, 2024
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Development of on-resin cyclic tetrazine libraries for isolating inhibitor of KRas (G12V) -Sos interaction, via proximity-catalyzed Inverse Electron Demand Diels-Alder.
Clark University
Aug. 15, 2020
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Recipient
AAUW
2020
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Recipient
Clark University
2020
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Hodgkins Junior Faculty award
Clark University
2021
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Nominee, President’s Achievement Awards for Inclusive Excellence
Clark University
2022
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Invited lecture
College of the Holy Cross
2023
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Invited lecture
Wayne State University
2023
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Speaker, American Peptide Society
American Peptide Society
2023
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American Peptide Society committee member
American Peptide Society
2023
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Invited lecture
University of Massachusetts Lowell
2023
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Recipient, Faculty Grant Incentive Award, 2023-24, Clark University
Clark University
2023
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