Aflatoxin B₁ (AFB₁) and sterigmatocystin (ST) are mycotoxins that pose significant threats to human and animal health owing to their mutagenic, carcinogenic, and toxic properties. They are structurally similar and widely believed to exert their biological effects via the generation of DNA-damaging epoxides at their respective terminal furan rings. Despite structural identity in the warhead portion of each toxin, this work shows that distal parts of each molecule are responsible for the distinctive mutational fingerprints seen in gptΔ C57BL/6J mouse embryo fibroblasts (MEFs). The two toxins differ structurally in the puckered cyclopentenone ring of AFB₁ and in the planar xanthone functionality of ST. While both toxins mainly induce GC→TA mutations, the aforementioned differences in structure apparently trigger unique patterns of mutations, as revealed by high-resolution duplex sequencing of MEF genomes. AFB₁ is more mutagenic than ST and displays its transversion mutations in a pattern with primary and secondary hotspots (underscored) in 5′-CGC-3′ and 5′-CGG-3′ contexts, respectively. ST displays a modest 5′-CGG-3′ hotspot while its other GC→TA transversions are more uniformly distributed in a pattern resembling established oxidative stress mutational spectra. This research delineates the mutational spectra of AFB₁ and ST, establishing these patterns as possible early-onset biomarkers of exposure.

The mannose cap motif, which consists of short-chain α(1,2)- d-mannans located on the non-reducing end of Mycobacterium tuberculosis ’ mannose-capped lipoarabinomannan (ManLAM), exhibits strong binding affinities toward the lectins on mammalian host cells. The α(1,2)- d -mannans induce the immunosuppressive effects crucial for the survival and virulence of mycobacteria. However, the biological activities of discrete α(1,2)- d-mannans with different chain lengths remain unknown. In this study, the rapid synthesis of α(1,2)-d-mannans was rationally developed to increase the accessibility of α(1,2)-d-mannans. The rapid synthesis enabled simultaneous productions of the protected α(1,2)-d -mannans with chain lengths of 2–5 units, at room temperature (25 °C), within 4 h. After hydrolysis unmasking, different sizes of α(1,2)- d-mannans, and their α(1,6)-d -mannan counterparts were obtained and biologically evaluated. In summary, this work led to the optimally-designed low-steric-hindrance bicyclic orthoester monomer suitable for the gram-scale rapid synthesis of α(1,2)- d-mannans at 25 °C. This provided a basis for further development of more efficient syntheses for glycans with (1,2)-glycosidic linkages. Notably, the improved accessibility to these glycan motifs allowed us to discover that the α(1,2)-d -mannobioside could significantly enhance LPS-induced nitric oxide production in macrophages, suggesting its potential use as an immunomodulator and implying the existence of an unknown pathway or receptor responsible for this effect.