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An indole-rich tripodal microtubule inhibitor is designed, which binds at the DCVJ site of tubulin and inhibits its polymerization. It causes apoptotic death of cancer cells without affecting normal cells and inhibits the growth of tumors. Finally, STD-NMR and TR-NOESY experiments reveal that the indole appendages play a crucial role in interacting with tubulin. [ABSTRACT FROM AUTHOR]

A matrix metalloproteinase (MMP) targeted tetrapeptide vesicle has been designed and developed, which strongly binds at a MMP9 enzymatic site. Interestingly, it has a 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. [ABSTRACT FROM AUTHOR]

The fluorescence dynamics of Photosystem I (PSI) in bulk water and inside a confined environment like a liposome have been investigated using time resolved confocal microscopy. In bulk water, PSI exhibits a major emission peak at ∼680 nm, while in the liposome it exhibits a markedly blue shifted emission maximum at ∼485 nm. This is indicative of conformational changes due to entrapment and emergence of a stressed conformation of PSI inside the liposome. The observed time constants for the fluorescence lifetime of PSI inside the liposome are significantly high as opposed to PSI in bulk water. More interestingly, the fluorescence intensity of PSI in bulk water exhibits strong fluctuations with many high intensity jumps and these are anti-correlated with the fluorescence lifetime of PSI. In contrast, inside the liposome, no such anti-correlated behaviour is observed. We further demonstrated that PSI exhibits at least two conformational states in bulk water, whereas a single conformation is observed inside the liposome, indicating the conformational rigidity and locking of the PSI complex inside a liposome. [ABSTRACT FROM AUTHOR]

An antimitotic cell penetrating octapeptide containing single Arg amino acid is discovered, which strongly binds with the exchangeable GTP/GDP binding site of tubulin, inhibits tubulin polymerization, reduces kinesin driven microtubule motility, activates apoptotic and mitotic check point proteins, induces apoptotic death and significantly inhibits the multicellular tumor spheroid growth of HeLa cells. [ABSTRACT FROM AUTHOR]

A tumor-like multi-cellular spheroid (3D) differs from a 2D cell in a number of ways. This is demonstrated using time resolved confocal microscopy. Two different tumor spheroids – HeLa (cervical cancer) and A549 (lung cancer) – are studied using 3 different fluorescent dyes – C153 (non-covalent), CPM (covalent) and doxorubicin (non-covalent, anti-cancer drug). The pattern of localization of these three fluorescent probes in the 3D tumor cell exhibits significant differences from that in the conventional 2D cells. For both the cells (HeLa and A549), the total uptake of doxorubicin in the 3D cell is much lower than that in the 2D cell. The uptake of doxorubicin molecules in the A549 spheroid is significantly different compared to the HeLa spheroid. The local polarity (i.e. emission maxima) and solvation dynamics in the 3D tumor cell differ from those in 2D cells. The covalent probe CPM exhibits intermittent fluorescence oscillations in the 1–2 s time scale. This is attributed to redox processes. These results may provide new insights into 3D tumors. [ABSTRACT FROM AUTHOR]

The fluorescence dynamics of Photosystem I (PSI) in bulk water and inside a confined environment like a liposome have been investigated using time resolved confocal microscopy. In bulk water, PSI exhibits a major emission peak at ∼680 nm, while in the liposome it exhibits a markedly blue shifted emission maximum at ∼485 nm. This is indicative of conformational changes due to entrapment and emergence of a stressed conformation of PSI inside the liposome. The observed time constants for the fluorescence lifetime of PSI inside the liposome are significantly high as opposed to PSI in bulk water. More interestingly, the fluorescence intensity of PSI in bulk water exhibits strong fluctuations with many high intensity jumps and these are anti-correlated with the fluorescence lifetime of PSI. In contrast, inside the liposome, no such anti-correlated behaviour is observed. We further demonstrated that PSI exhibits at least two conformational states in bulk water, whereas a single conformation is observed inside the liposome, indicating the conformational rigidity and locking of the PSI complex inside a liposome.