The Influence of the Amide Linkage in the Fe(III) -Binding Properties of Catechol-Modified Rosamine Derivatives.

The two new fluorescent ligands RosCat1 and RosCat2 contain catechol receptors connected to rosamine platforms through an amide linkage and were synthesized by using microwave-assisted coupling reactions of carboxyl- or amine-substituted rosamines with the corresponding catechol units and subsequent deprotection. RosCat1 possesses a reverse amide, whereas RosCat2 has the usual oriented amide bond (HNCO vs. CONH, respectively). The ligands were characterized by means of NMR spectroscopy, mass-spectrometry, and DFT calculations and X-ray crystallography studies for RosCat1. The influence of the amide linkage on the photophysical properties of the fluorescent ligands was assessed in different solvents and showed a higher fluorescence quantum yield for RosCat1. The coordination chemistry of these ligands with a Fe(III) center has been rationalized by mass-spectrometric analysis and semiempirical calculations. Octahedral Fe(III) complexes were obtained by the chelation of three RosCat1 or RosCat2 ligands. Interestingly, the unconventional amide connectivity in RosCat1 imposes the formation of an eight-membered ring on the chelate complex through a "salicylate-type" mode of coordination.

Glycoproteogenomics: Setting the Course for Next-generation Cancer Neoantigen Discovery for Cancer Vaccines.

Molecular-assisted precision oncology gained tremendous ground with high-throughput next-generation sequencing (NGS), supported by robust bioinformatics. The quest for genomics-based cancer medicine set the foundations for improved patient stratification, while unveiling a wide array of neoantigens for immunotherapy. Upfront pre-clinical and clinical studies have successfully used tumor-specific peptides in vaccines with minimal off-target effects. However, the low mutational burden presented by many lesions challenges the generalization of these solutions, requiring the diversification of neoantigen sources. Oncoproteogenomics utilizing customized databases for protein annotation by mass spectrometry (MS) is a powerful tool toward this end. Expanding the concept toward exploring proteoforms originated from post-translational modifications (PTMs) will be decisive to improve molecular subtyping and provide potentially targetable functional nodes with increased cancer specificity. Walking through the path of systems biology, we highlight that alterations in protein glycosylation at the cell surface not only have functional impact on cancer progression and dissemination but also originate unique molecular fingerprints for targeted therapeutics. Moreover, we discuss the outstanding challenges required to accommodate glycoproteomics in oncoproteogenomics platforms. We envisage that such rationale may flag a rather neglected research field, generating novel paradigms for precision oncology and immunotherapy.