Sri Kamesh Narasimhan

5^th year Ph.D. Candidate (expected 2010)

 

Contact Information

Prof. Yan-Yeung Luk Laboratory, 1-014

Department of Chemistry, Syracuse University

Syracuse NY 13244-4100

E-mail: snaras01@syr.edu

Phone: 315-443-5810 (lab), 315-569-1681 (cell)

 

Thesis

Structured Unnatural Molecules: Inducing Molecular Folding and Enabling Matured Mammalian Cell Adhesion

 

Education

· 2004 - Present: Ph.D. candidate, Syracuse University, Syracuse, New York

· 2001-1999: MSc in Chemistry, Sri Sathya Sai University, Andhra Pradesh, India

· 1999-1996: BSc (Honors), Sri Sathya Sai University, Andhra Pradesh, India

 

Research Projects

 

1)  Design and synthesis of C₃ dissymmetric bowls that induce molecular folding

 

Folding at the molecular level is an interesting phenomenon that involves multiple interactions, covalent and non-covalent, that help guide a complex molecule to assemble into a defined three dimensional structural unit. To replicate this natural phenomenon, we have designed and synthesized a non-natural C₃-disymmetric bowl-shaped core on which amino acids, when substituted at the periphery, give rise to two disatereomers that adopt a “protein-like” folded conformation. Considering the large conformational ensembles that are possible for these two molecules, these structures resemble mini proteins with only three amino acid residues. We believe the C₃-symmetric bowl-shaped core, with its three tethered amino acids, to be the smallest known motifs that fold into a well defined three dimensional structure. These folded chiral bowl-shaped molecules further have the potential for mimicking the active sites of proteins and for assembling into novel supramolecular structures.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

“Induced Folding by Chiral Non-Planar Aromatics.” Sri Kamesh Narasimhan, Deborah J.  Kerwood, Lei Wu, Jun Li, Yongbin Han, Shifa Zhu, Akshay Shah, Rosina Lombardi, Teresa B. Freedman* and Yan-Yeung Luk* J. Org.  Chem. 2009, 74, 7023–7033.†

 

 

2) Enhanced mammalian cell adhesion on surfaces mediated by squarates

 

The discovery of small, uniquely folded unnatural molecules that mediate selective cell adhesion on surfaces are critical for engineering “living biomaterials” that are compatible with human tissue. To achieve this objective, we chose to simulate the RGD-Integrin recognition and binding event that precedes the cell adhesion. We have designed and synthesized RGD mimics based on the squarate backbone (called squaramides) that are presented on self-assembled monolayers (SAMs) of alkanethiolates on gold films. The squaramide derivatives immobilized on surfaces provide enhanced cell adhesion, attachment and matured growth in mammalian cells. These results are significant as they demonstrate the use of an abiotic moiety that mimics RGD ligand and stimulates cell attachment, growth and proliferation rather than inhibiting cell adhesion. 

 

“Mature Mammalian Cell Adhesion and Enhanced Signaling Induced by Squaramide Ligands.” Sri Kamesh Narasimhan, Preeti Sejwal, Shifa Zhu and Yan-Yeung Luk* Submitted.

 

“Selective Immobilization of Peptides Exclusively via N-Terminus Cysteines by Water-Driven Reactions on Surfaces.” Preeti Sejwal, Sri Kamesh Narasimhan, Deepali Prashar, Debjyoti Bandyopadhyay and Yan-Yeung Luk* J. Org. Chem. 2009, 74, 6843–6846.

 

 

3) Theoretical design of Highly Symmetric Chiral Molecules with T, O or I Symmetry

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Since the birth of stereochemistry in the early 19^th century and the subsequent development and use of symmetry point groups to describe chirality, there has been an essentially open but a difficult problem: the symmetry groups T, O and I have existed theoretically, but there has been no molecule that is real or imaginary that has rigorously fulfilled the requirements of these symmetry point groups. Most texts tend to avoid mentioning these high symmetry polyhedral point groups and do not even acknowledge their possibility of existence. To overcome this limitation, there have been several attempts in the past century, including some by Nobel laureates, to design these unusual symmetry groups that are otherwise expressed in art and are ubiquitous in nature.  Until now, the design and synthesize of T symmetric molecules has only come about through non-covalent or gas-phase chemistry. We have designed covalently-based molecules that permanently and rigorously satisfy the requirements imposed by these symmetry point groups and are not based on some transient conformations.

 

“Chiral Molecules with Polyhedral T, O or I Symmetry: Theoretical Solution to a Difficult Problem in Stereochemistry.” Sri Kamesh Narasimhan, Xiaoying Lu and Yan-Yeung Luk* Chirality 2008, 20, 878-884.