The Peptides/peptide nucleic acids (PNAs) are synthesized by the solid phase peptide synthesis (SPPS) followed by purification by analytic or semi-preparative HPLCs (Agilent/Shimadzu/Waters). Furthermore, the synthesized molecules are confirmed by MALDI-TOF/ESI mass spectrometry (Bruker). Some PNAs are incorporated with the pre-synthesized non-canonical nucleobases. The synthesized Peptides/PNAs have huge implications in the chemical biology/medical biology fields in near futures. (Publication article #9, #10, and #24 for more details)
Schemes
The designed synthesized targeted molecules have validated in the cell-free as well in cell systems. The molecules exhibited excellent importance towards the key cell regulatory organelle microtubules. It exhibits the significant disruption of microtubules confirmed by various bio-physical assays (turbidity, MT assembly assay, FRET, MT gliding assays etc). After successful interaction via bio physical studies, the MT interactions with synthesized molecules confirmed by cell based assays (immunofluorescence, morphology, apoptosis, and cell cycle etc). Moreover, the interactions have also been confirmed by 3D cellular spheroid formation.
The melanoma cancer cells are over-expresses with surface receptors, integrin, epinephrine. The dual functional liposome designed and synthesized targeted to melanoma cells through integrin and ephrin receptors (LC-LDV, LC-YSA). (Publication article #14, #10, #22 for more details)
I have worked on the design and modification of non-canonical nucleobases based on triazine moiety. The synthesized nucleobases successfully interacts with thymine/uracil via bifacial triplex formation (T-M-T/U-M-U). the bifacial PNAs consisted with native and nan-native nucleobases strongly interact with over expressed genes (like MALAT1) and may down regulate its expression. The interactions between them have been revealed by various bio-physical assays thermal denaturation assay (Tm), circular dichroism (CD), Electrophoretic Mobility-Shift Assay (EMSA). The delivery of the bPNAs have also been checked by cell based studies. (Publication article #21, and #22 for more details)
Bi-facial Peptide-nucleic acid (bPNA) and DNA/RNA interaction unraveled by Thermal melting assay
Electrophoretic mobility shift assay (EMSA) PNA-DNA/RNA Interaction Heatmap Analysis
The antigen, and antibody are fundamentally proteins which has significant importance in the field of therapeutics and development of new antibody-drug conjugates. The structure and the dynamics of antigen-antibody, the antigen is enhanced GFP (EGFP) and the antibody is anti-EGFP VHH-His6 has been unraveled by various advanced techniques, circular dichroism (CD) spectroscopy, fluorescence correlation spectroscopy (FCS) and single molecule FRET (smFRET). Moreover, the effect of pH changes on the antigen-antibody complexes have been revealed. Overall study determines that the structure of the antigen–antibody complex is dynamic in nature and is not rigid. (publication article #5 for more details)
The superior cell penetrating peptides and designing of some peptide vesicles have been investigated for the potential delivery vehicles. However, the tryptophan-tryptophan (W-W) rich short peptides have the potential to cell penetrate and rich up to cell nucleus. The liposomal lipopeptide (long chain attached short peptide) are able to deliver the drugs successfully inside the cellular nucleus. The successful reduction/inhibition of tumor growth in mice model has been investigated.
the short tetrapeptide (His-Tryp-Gly-Phe) significantly constructs the peptide vesicles and it has the propensity to encapsulate and deliver the doxorubicin drug specifically to the cancer cell, induces superior apoptotic death, and inhibits the metastatic cancer cell migration and growth of multicellular 3D spheroids. The peptide vesicles has been confirmed by the atomic force microscopy (AFM), fluorescence microscopy. (publication article #15 for more details)
Applying various approaches to synthesize DNA based on enzymatic approach, avoiding chemical pathway. The aim is to adopt efficient, easier, and in template-independent DNA synthesis.
Synthetic biology & Nucleic acid modification based on Copper free click chemistry, Bio-conjugation, & Co-polymerization chemistry approach
Molecular-Chemo-genetics (A/C mutagenesis chemically & Enzymatically)
Potential Repository system development applying Chemical & Biological approach