Doctor of Philosophy, Jadavpur University (2013)
Bachelor of Science, Vidyasagar University (2006)
Master of Science, Indian Institute of Technology, Roorkee (2008)
James Chen, Postdoctoral Faculty Sponsor
Dynamic and Responsive DNA-like Polymers
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2018; 140 (42): 13594–98
The synthesis of thiolactone monomers that mimic natural nucleosides and engage in robust ring opening polymerizations (ROP) is herein described. As each repeat unit contains a thioester functional group, dynamic rearrangement of the polymer is feasible via thiol-thioester exchange, demonstrated here by depolymerization of the polymers and coalescing of two polymers of different molecular weight or chemical composition. This approach constitutes the first step toward a platform that enables for the routine synthesis of sequence controlled polymers via dynamic template directed synthesis.
View details for DOI 10.1021/jacs.8b09105
View details for Web of Science ID 000448755200016
View details for PubMedID 30351134
Internal Oligoguanidinium-Based Cellular Transporter Enhances Antisense Efficacy of Morpholinos in In Vitro and Zebrafish Model
2016; 27 (10): 2254-2259
An efficient cellular transporter is highly desirable for the therapeutic applications of antisense phosphorodiamidate morpholino oligonucleotides (PMOs) as Vivo-PMO and PPMO have limitations for in vivo study. We report here a novel internally tetraguanidinium-linked nonpeptidic cellular transporter having a conformationally rigid backbone composed of pharmacologically compatible heterocyclic six-membered rings which internalizes efficiently into cells in full growth medium and ubiquitously distributed into zebrafish embryos. It efficiently transports antisense PMO in vitro and in vivo zebrafish embryos. Comparative study with Gene Tools Vivo-PMO revealed that our cellular-transporter conjugated PMO shows better antisense efficacy.
View details for DOI 10.1021/acs.bioconjchem.6b00252
View details for Web of Science ID 000385992000004
View details for PubMedID 27625020
Piperazic acid derivatives inhibit Gli1 in Hedgehog signaling pathway
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
2016; 26 (18): 4423-4426
Piperazic acid, a non-proteinogenic amino acid, found in complex secondary metabolites and peptide natural substances, has shown down regulation of Gli1 expression in Hedgehog signaling pathway in cell based assays. Further structure activity relationship study indicated that amide derivatives of piperazic acid are more potent than piperazic acid itself, with little to no toxicity. However, other cellular components involved in the pathway were not affected. To the best of our knowledge, this is the first report on the inhibitory property of piperazic acid in this pathway. Hence, this molecule could serve as a useful tool for studying Hedgehog signaling.
View details for DOI 10.1016/j.bmcl.2016.08.008
View details for Web of Science ID 000382263800007
View details for PubMedID 27528433
Clickable Nucleic Acids: Sequence- Controlled Periodic Copolymer/ Oligomer Synthesis by Orthogonal Thiol-X Reactions
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2015; 54 (48): 14462-14467
Synthetic polymer approaches generally lack the ability to control the primary sequence, with sequence control referred to as the holy grail. Two click chemistry reactions were now combined to form nucleobase-containing sequence-controlled polymers in simple polymerization reactions. Two distinct approaches are used to form these click nucleic acid (CNA) polymers. These approaches employ thiol-ene and thiol-Michael reactions to form homopolymers of a single nucleobase (e.g., poly(A)n ) or homopolymers of specific repeating nucleobase sequences (e.g., poly(ATC)n). Furthermore, the incorporation of monofunctional thiol-terminated polymers into the polymerization system enables the preparation of multiblock copolymers in a single reaction vessel; the length of the diblock copolymer can be tuned by the stoichiometric ratio and/or the monomer functionality. These polymers are also used for organogel formation where complementary CNA-based polymers form reversible crosslinks.
View details for DOI 10.1002/anie.201506711
View details for Web of Science ID 000367724000047
View details for PubMedID 26458149