Development of bombesin-tubulysin conjugates using multicomponent chemistry to functionalize both the payload and the homing peptide.

Peptide-drug conjugates (PDCs) have recently gained significant attention for the targeted delivery of anticancer therapeutics, mainly due to their cost-effective and chemically defined production and lower antigenicity compared to ADCs, among other benefits. In this study, we designed and synthesized novel PDCs by conjugating new thiol-functionalized tubulysin analogs (tubugis) to bombesin, a peptide ligand with a relevant role in cancer research. Two tubulysin analogs bearing ready-for-conjugation thiol groups were prepared by an on-resin multicomponent peptide synthesis strategy and subsequently tested for their stand-alone anti-proliferative activity against human cancer cells, which resulted in IC values in the nanomolar range.

Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: Correlation with FDG-PET/CT.

The value of circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients has not yet been well established. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high spatial and temporal heterogeneity. Although ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker.

Advancing Multicomponent Strategies to Macrobicyclic Peptides.

Macrocyclization of peptides is typically used to fix specific bioactive conformations and improve their pharmacological properties. Recently, macrobicyclic peptides have received special attention owing to their capacity to mimic protein structures or be key components of peptide-drug conjugates. Here, we describe the development of novel synthetic strategies for two distinctive types of peptide macrobicycles.

On the CNK coordination modes in K[M(CN)]·xHO: first evidence of CNK electron-deficient bonding.

Based on the determination of single crystal XRD structures of potassium hexacyanidometallates and on IR, and Raman data, here we propose for the first time the occurrence of an electron-deficient bonding between the N end of the CN ligand and the K metal center. The crystal structures of K[M(CN)]·xHO (M = Fe(ii), Ru(ii), Os(ii), Co(iii), Rh(iii), Ir(iii), Pt(iv)) reveal the presence of four types of CNK interactions: (i) a linear CN-K bond, (ii) the N ends in a bipodal coordination involving two K atoms, (iii) the N ends in a tripodal coordination mode involving three K atoms and (iv) the N ends and the K atoms with the largest K-N distances within the subseries that can be attributed to the electrostatic interactions. The bi- and tripodal coordination modes between the N end of the CN ligand and K ions are atypical and their nature is discussed in this contribution.

CuCu and Ag-isocyanobenzoates as novel 1D semiconducting coordination oligomers.

Two novel semiconducting coordination oligomers with 1D chain structures, namely [H0.07 CuI0.65CuII0.