Unilateral, Sectoral Retinal Metastasis of Small-Cell Lung Cancer Mimicking Viral Retinitis.

PURPOSE: To report a case of unilateral, sectoral retinal metastasis of small-cell lung cancer (SCLC) that mimicked cytomegalovirus (CMV) retinitis. METHOD: Case report. RESULTS: A 48-year-old woman presented with a four-week history of a visual field loss in her right eye. She had a past medical history of extensive-stage SCLC with brain metastasis, stable on maintenance atezolizumab for two years. On initial presentation, she was diagnosed with CMV retinitis. No improvement was observed with 4 weeks of oral valganciclovir. Upon referral for a second opinion, her fundus exam appeared compatible with CMV retinitis, and anterior chamber tap for polymerase chain reaction for viral etiologies was performed followed by intravitreal and intravenous ganciclovir without improvement. She was referred for a third opinion, where diagnostic vitrectomy with vitreous and retinal biopsies were consistent with SCLC metastatic to the retina. The patient underwent enucleation of the right eye for definitive pathologic analysis and subsequently was started on additional systemic chemotherapy. CONCLUSION: Retinal metastases are exceedingly rare, particularly retinal metastasis of SCLC. Retinal metastasis should be considered in patients initially diagnosed with viral retinitis who fail to improve despite antiviral therapy, particularly if they have a known history of malignancy. Furthermore, retinal metastasis of SCLC potentially could be misdiagnosed histopathologically as retinoblastoma if the patient's history is unknown and appropriate immunohistochemical stains are not performed.

Peptide Carbocycles: From -SS- to -CC- via a Late-Stage "Snip-and-Stitch".

One way to improve the therapeutic potential of peptides is through cyclization. This is commonly done using a disulfide bond between two cysteine residues in the peptide. However, disulfide bonds are susceptible to reductive cleavage, and this can deactivate the peptide and endanger endogenous proteins through covalent modification. Substituting disulfide bonds with more chemically robust carbon-based linkers has proven to be an effective strategy to better develop cyclic peptides as drugs, but finding the optimal carbon replacement is synthetically laborious. We report a new late-stage platform wherein a single disulfide bond in a cyclic peptide can serve as the progenitor for any number of new carbon-rich groups, derived from organodiiodides, using a Zn:Cu couple and a hydrosilane. We show that this platform can furnish entirely new carbocyclic scaffolds with enhanced permeability and structural integrity and that the stereochemistry of the new cycles can be biased by a judicious choice in silane.

carba-Nucleopeptides (cNPs): A Biopharmaceutical Modality Formed through Aqueous Rhodamine†B Photoredox Catalysis.

Exchanging the ribose backbone of an oligonucleotide for a peptide can enhance its physiologic stability and nucleic acid binding affinity. Ordinarily, the eneamino nitrogen atom of a nucleobase is fused to the side chain of a polypeptide through a new C-N bond. The discovery of C-C linked nucleobases in the human transcriptome reveals new opportunities for engineering nucleopeptides that replace the traditional C-N bond with a non-classical C-C bond, liberating a captive nitrogen atom and promoting new hydrogen bonding and π-stacking interactions. We report the first late-stage synthesis of C-C linked carba-nucleopeptides (cNPs) using aqueous Rhodamine B photoredox catalysis. We prepare brand-new cNPs in batch, in parallel, and in flow using three long-wavelength photochemical setups. We detail the mechanism of our reaction by experimental and computational studies and highlight the essential role of diisopropylethylamine as a bifurcated two-electron reductant.