Faculty Biography

Arundhati Nag

Arundhati Nag, Ph.D.

Assistant Professor
Carlson School of Chemistry and Biochemistry
Clark University
Worcester, MA 01610

Email: anag@clarku.edu

Curriculum Vitae
Research Website


B.Sc. Kolkata University, 2004
M.Sc Indian Institute of Technology, Kanpur 2006
Ph.D. California Institute of Technology, 2013
Postdoctoral Fellow, California Institute of Technology 2013 - 2014
Staff Scientist, California Institute of Technology 2014 - 2017

Research Summary

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.

Recent Publications

1. Borges A. , Onasenko I. , Nag A.* Peptide Macrocycles: Methods and Protocol. Coppock MB, Winton AJ, editors. Washington DC: Springer .Forthcoming: October 11, 2021 ISBN 978-1-0716-1688-8

2. Nag, A*, Das, S. Fluorescence sensing of phosphate containing biomolecules, Israel Journal of Chemistry. 61 (3-4), 169-184 (2021)

3. Kandler, R., Das, S., Nag, A.* Copper-ligand clusters dictate size of cyclized peptide formed during alkyne-azide cycloaddition on solid support. RSC. Advances. 11, 4842- 4850, (2021)

4. Borges A, Gillespie D, Nag A.* Biological applications of amide and amino acid containing synthetic macrocycles. Supramolecular Chemistry. 31(8), 575-596 (2019). Special issue “Emerging Supramolecular Chemists in North America”

5. Ul-Ain Q., Kandler R., Gillespie D, Nag A.* Chemical Epitope Targeting: Review of a Novel Screening Technology. Journal of Medicinal Chemistry and Drug Design. 1(2), 1-7 (2018).

6. Nag, A., Das, S. Provisional patent 63/075, 630, Filed September 8, 2020

7. Henning RK, Varghese JO, Das S, Nag A, Tang G, Tang K, Sutherland AM, Heath JR. Degradation of Akt using protein-catalyzed capture agents. J Pept Sci. 22(4), 196-200 (2016).

8. Das S#, Nag A#, Liang J, Bunck DN, Umeda A, Farrow B, Coppock MB, Sarkes DA, Finch AS, Agnew HD, Pitram S, Lai B, Yu MB, Museth AK, Deyle KM, Lepe B, Rodriguez-Rivera FP, McCarthy A, Alvarez-Villalonga B, Chen A, Heath J, Stratis-Cullum DN, Heath JR. A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands. Angew Chem Int Ed Engl. 54(45), 13219-13224 (2015). (#equal contribution)

9. Farrow B, Wong M, Malette J, Lai B, Deyle KM, Das S, Nag A, Agnew HD, Heath JR. Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin. Angew Chem Int Ed Engl. 54(24), 7114-7119 (2015).

10. Deyle KM, Farrow B, Qiao Hee Y, Work J, Wong M, Lai B, Umeda A, Millward SW, Nag A, Das S, Heath JR. A protein-targeting strategy used to develop a selective inhibitor of the E17K point mutation in the PH domain of Akt1. Nat Chem. 7(5), 455-462 (2015).

11. Nag A, Das S, Yu MB, Deyle KM, Millward SW, Heath JR. A chemical epitope-targeting strategy for protein capture agents: the serine 474 epitope of the kinase Akt2. Angew Chem Int Ed Engl. 52(52), 13975-13979 (2013).

12. Millward SW, Agnew HD, Lai B, Lee SS, Lim J, Nag A, Pitram S, Rohde R, Heath JR. In situ click chemistry: from small molecule discovery to synthetic antibodies. Integr Biol (Camb). 5(1), 87-95 (2013).

13. Millward SW, Henning RK, Kwong GA, Pitram S, Agnew HD, Deyle KM, Nag A, Hein J, Lee SS, Lim J, Pfeilsticker JA, Sharpless KB, Heath JR. Iterative in situ click chemistry assembles a branched capture agent and allosteric inhibitor for Akt1. J. Am Chem Soc. 133(45),18280-18288 (2011).

14. Agnew, HD, Rohde RD, Millward SW, Nag A, Yeo WS, Hein JE, Pitram SM, Tariq AA, Burns VM, Krom RJ, Fokin VV, Sharpless KB, Heath JR. Iterative in situ click chemistry creates antibody-like protein-capture agents. Angew Chem Int Ed Engl. 48(27), 4944-4948 (2009).