Diversity is the key: Skeletal diversity is a useful starting point in the search for compounds that modulate protein–biopolymer interactions. A library of 400 lactam carboxamides has been synthesized in a short synthetic sequence and a new compound that inhibits the interaction of a transcription factor (HOXA13) with its DNA target has been discovered, and inhibition of transcription is demonstrated in cells.
All cells expel a variety of nano-sized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells’ biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application. Yet, it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here we demonstrate peptide binding to tumor-associated EVs via overexpressed membrane protein. We find that SKOV-3 ovarian tumor cells and their released EVs express α3β1 integrin, which can be targeted by our in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enabled us to differentiate cancer-associated exosomes from non-cancer exosomes. Furthermore, we introduce the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30. LXY30 not only exhibits high specificity and affinity to α3β1 integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.
This Communication describes a cascade reaction sequence that leads to highly functionalized cyclohexenones starting from reaction of cyclobutenones with alpha-lithio-alpha,beta-unsaturated sulfones and amides. The hexatriene-cyclohexadiene cyclization steps presumed to be involved in these transformations are among the most facile hexatriene electrocyclizations reported thus far.
Raman scattering
provides stable narrow-banded signals that potentially
allow for multicolor microscopic imaging. The major obstacle for the
applications of Raman spectroscopy and microscopy is the small cross
section of Raman scattering that results in low sensitivity. Here,
we report a new concept of azo-enhanced Raman scattering (AERS) by
designing the intrinsic molecular structures using resonance Raman
and concomitant fluorescence quenching strategies. Based on the selection
of vibrational modes and the enhancing unit of azobenzenes, we obtained
a library of AERS molecules with specific Raman signals in the fingerprint
and silent frequency regions. The spectral characterization and molecular
simulation revealed that the azobenzene unit conjugated to the vibrational
modes significantly enhanced Raman signals due to the mechanism of
extending the conjugation system, coupling the electronic–vibrational
transitions, and improving the symmetry of vibrational modes. The
nonradiative decay of azobenzene from the excited state quenched the
commitment fluorescence, thus providing a clean background for identifying
Raman scattering. The most sensitive AERS molecules produced Raman
signals of more than 4 orders of magnitude compared to 5-ethynyl-2′-deoxyuridine
(EdU). In addition, a frequency tunability of 10 distinct Raman bands
was achieved by selecting different types of vibrational modes. This
methodology of AERS allows for designing small-molecule Raman probes
to visualize various entities in complex systems by multicolor spontaneous
Raman imaging. It will open new prospects to explore innovative applications
of AERS in interdisciplinary research fields.
Substituted maleic anhydrides react with imines to form polycyclic lactam products. Diastereoselectivity can be controlled by altering the reaction conditions in some cases, and regiochemistry is dictated by the structure of the allylic substituents on the anhydride. Cyclic imines, including dihydro-beta-carbolines and dihydroisoquinolines, exhibit the highest level of reactivity in these new annulation reactions.
Super-capacity information-carrying systems are fabricated by tuning vibrational signals into octal numeral intensities in multiple bands of Raman-silent regions.
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