7 research outputs found
Cascade photocaging of diazeniumdiolate: a novel strategy for one and two photon triggered uncaging with real time reporting
We report a new strategy, viz. cascade photocaging, for protecting diethylamine diazeniumdiolate (O2-position), a light sensitive molecule. Upon photolysis, the cascade photocage at first releases the light activatable linker (latent fluorophore) O2-caged diazeniumdiolate, which undergoes spontaneous 1,8-elimination, triggering the release of the diazeniumdiolate anion and the fluorophore
Three-arm, biotin-tagged carbazole-dicyanovinyl-chlorambucil conjugate: simultaneous tumor targeting, sensing, and photoresponsive anticancer drug delivery
The design, synthesis and in vitro biological studies of a biotin-carbazole-dicyanovinyl-chlorambucil conjugate (Bio-CBZ-DCV-CBL; 6) are reported. This conjugate (6) is a multifunctional single-molecule appliance composed of a thiol-sensor DCV functionality, a CBZ-derived phototrigger as well as fluorescent reporter and CBL as the anticancer drug and Bio as the cancer-targeting ligand. In conjugate 6, the DCV bond undergoes a thiol-ene click reaction at pH<7 with intracellular thiols, thereby shutting down internal charge transfer between the donor CBZ and acceptor DCV units, resulting in a change of the fluorescence color from green to blue, and thereby, sensing the tumor microenvironment. Subsequent photoirradiation results in release of the anticancer drug CBL in a controlled manner
Photocaging of Single and Dual (Similar or Different) Carboxylic and Amino Acids by Acetyl Carbazole and its Application as Dual Drug Delivery in Cancer Therapy
A new fluorescent photoremovable
protecting group (FPRPG) based
on acetylcarbazole framework has been explored for the first time
release of single and dual (similar or different) substrates from
single chromophore. Mechanistic studies of the photorelease process
revealed that photorelease of two (similar or different) substrates
from acetyl carbazole proceeds via a stepwise pathway. Further, we
constructed photoresponsive dual drug delivery system (DDS) to release
two different anticancer drugs (caffeic acid and chlorambucil, 1 equiv
each). In vitro study reveals that our DDS exhibit excellent properties
like biocompatibility, cellular uptake, and photoregulated dual drug
release
One- and Two-Photon Uncaging: Carbazole Fused <i>o</i>‑Hydroxycinnamate Platform for Dual Release of Alcohols (Same or Different) with Real-Time Monitoring
A one- and two-photon
activated photoremovable protecting group
(PRPG) was designed based on a carbazole fused <i>o</i>-hydroxycinnamate
platform for the dual (same or different) release of alcohols. The
mechanism for the dual release proceeds through a stepwise pathway
and also monitors the first and second photorelease in real time by
an increase in fluorescence intensity and color change, respectively.
Further, its application in staining live neurons and ex vivo imaging
with two-photon excitation is shown
Engineered RecA Constructs Reveal the Minimal SOS Activation Complex
The
SOS response is a bacterial DNA damage response pathway that
has been heavily implicated in bacteria’s ability to evolve
resistance to antibiotics. Activation of the SOS response is dependent
on the interaction between two bacterial proteins, RecA and LexA.
RecA acts as a DNA damage sensor by forming lengthy oligomeric filaments
(RecA*) along single-stranded DNA (ssDNA) in an ATP-dependent manner.
RecA* can then bind to LexA, the repressor of SOS response genes,
triggering LexA degradation and leading to induction of the SOS response.
Formation of the RecA*-LexA complex therefore serves as the key “SOS
activation signal.” Given the challenges associated with studying
a complex involving multiple macromolecular interactions, the essential
constituents of RecA* that allow LexA cleavage are not well defined.
Here, we leverage head-to-tail linked and end-capped RecA constructs
as tools to define the minimal RecA* filament that can engage LexA.
In contrast to previously postulated models, we found that as few
as three linked RecA units are capable of ssDNA binding, LexA binding,
and LexA cleavage. We further demonstrate that RecA oligomerization
alone is insufficient for LexA cleavage, with an obligate requirement
for ATP and ssDNA binding to form a competent SOS activation signal
with the linked constructs. Our minimal system for RecA* highlights
the limitations of prior models for the SOS activation signal and
offers a novel tool that can inform efforts to slow acquired antibiotic
resistance by targeting the SOS response