A stereodefined approach towards the bicyclo[3.3.1]nonan-9-one core of the phloroglucin natural products guttiferone A and hypersampsone F

An approach towards the highly functionalized bicyclo[3.3.1]nonan-9-one core present in the phloroglucin natural products guttiferone A and hypersampsone F is disclosed in which the key C7 and C8 stereogenic centres have been successfully installed

A stereodefined approach towards the bicyclo[3.3.1]nonan-9-one core of the phloroglucin natural products guttiferone A and hypersampsone F

An approach towards the highly functionalized bicyclo[3.3.1]nonan-9-one core present in the phloroglucin natural products guttiferone A and hypersampsone F is disclosed in which the key C7 and C8 stereogenic centres have been successfully installed

Targeting PD-1/PD-L1 in cancer immunotherapy: An effective strategy for treatment of triple-negative breast cancer (TNBC) patients

Maintaining the balance between eliciting immune responses against foreign proteins and tolerating self-proteins is crucial for maintenance of homeostasis. The functions of programmed death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) are to inhibit immune responses so that over-reacting immune cells does not cause any damage to its own body cells. However, cancer cells hijack this mechanism to attenuate immune cells functions and create an immunosuppressive environment that fuel their continuous growth and proliferation. Over the past few years’ rapid development in cancer immunotherapy has opened a new avenue in cancer treatment. Blockade of PD-1 and PD-L1 has become a potential strategy that rescue the functions of immune cells to fight against cancer with high efficacy. Initially, immune checkpoint monotherapies were not very successful, making breast cancer less immunogenic. Although, recent reports support the presence of tumor infiltrating lymphocytes (TILs) in breast cancer that make it favorable for PD-1/PD-L1 mediated immunotherapy, which is effective in PD-L1 positive patients. Recently, anti-PD-1 (pembrolizumab) and anti-PD-L1 (atezolizumab) gets FDA approval for breast cancer treatment and make PD-1/PD-L1 immunotherapy is meaningful for further research. Likewise, this article gathered understanding of PD-1 and PD-L1 in recent years, their signaling networks, interaction with other molecules, regulations of their expressions and functions in both normal and tumor tissue microenvironments are crucial to find and design therapeutic agents that block this pathway and improve the treatment efficacy. Additionally, authors collected and highlighted most of the important clinical trial reports on monotherapy and combination therapy

Dual Fluorescence in GFP Chromophore Analogues: Chemical Modulation of Charge Transfer and Proton Transfer Bands

Dual fluorescence of GFP chromophore analogues has been observed for the first time. OHIM (<i>o</i>-hydroxy imidazolidinone) shows only a charge transfer (CT) band, CHBDI (<i>p</i>-cyclicamino <i>o</i>-hydroxy benzimidazolidinone) shows a comparable intensity CT and PT (proton transfer) band, and MHBDI (<i>p</i>-methoxy <i>o</i>-hydroxy benzimidazolidinone) shows a higher intensity PT band. It could be shown that the differential optical behavior is not due to conformational variation in the solid or solution phase. Rather, control of the excited state electronic energy level and excited state acidity constant by functional group modification could be shown to be responsible for the differential optical behavior. Chemical modification-induced electronic control over the relative intensity of the charge transfer and proton transfer bands could thus be evidenced. Support from single-crystal X-ray structure, NMR, femtosecond to nanosecond fluorescence decay analysis, and TDDFT-based calculation provided important information and thus helped us understand the photophysics better

Ultrafast Dynamics of a Green Fluorescent Protein Chromophore Analogue: Competition between Excited-State Proton Transfer and Torsional Relaxation

The competition between excited-state proton transfer (ESPT) and torsion plays a central role in the photophysics of fluorescent proteins of the green fluorescent protein (GFP) family and their chromophores. Here, it was investigated in a single GFP chromophore analogue bearing <i>o</i>-hydroxy and <i>p</i>-diethylamino substituents, OHIM. The light-induced dynamics of OHIM was studied by femtosecond transient absorption spectroscopy, at different pH. We found that the photophysics of OHIM is determined by the electron-donating character of the diethylamino group: torsional relaxation dominates when the diethylamino group is neutral, whereas ultrafast ESPT followed by cis/trans isomerization and ground-state reprotonation are observed when the diethylamino group is protonated and therefore inactive as an electron donor