We have determined the structure of a PNA-DNA duplex to 1.7 Å resolution by multiplewavelength anomalous diffraction on a zinc derivative. This structure represents the first highresolution view of a hybrid duplex containing a contiguous chiral PNA strand with complete γ-backbone modification ("γPNA"). Unlike the achiral counterpart, which adopts a random-fold, this particular γPNA is already preorganized into a right-handed helix as a single strand. The new structure illustrates the unique characteristics of this modified PNA, possessing conformational flexibility while maintaining sufficient structural integrity to ultimately adopt the preferred Phelical conformation upon hybridization with DNA. The unusual structural adaptability found in the γPNA strand is crucial for enabling the accommodation of backbone modifications while constraining conformational states. In conjunction with NMR analysis characterizing the structures and substructures of the individual building blocks, these results provide unprecedented insights into how this new class of chiral γPNA is preorganized and stabilized, before and after hybridization with a complementary DNA strand. Such knowledge is crucial for the future design and development of PNA for applications in biology, biotechnology and medicine.

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This paper presents a comprehensive review of European Union (EU) legislation addressing the safety of chemical substances, and possibilities within each piece of legislation for applying grouping and read-across approaches for the assessment of nanomaterials (NMs). Hence, this review considers both the overarching regulation of chemical substances under REACH (Regulation (EC) No 1907/2006 on registration, evaluation, authorization, and restriction of chemicals) and CLP (Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures) and the sector-specific pieces of legislation for cosmetic, plant protection and biocidal products, and legislation addressing food, novel food, and food contact materials. The relevant supporting documents (e.g. guidance documents) regarding each piece of legislation were identified and reviewed, considering the relevant technical and scientific literature. Prospective regulatory needs for implementing grouping in the assessment of NMs were identified, and the question whether each particular piece of legislation permits the use of grouping and read-across to address information gaps was answered.ARTICLE HISTORY

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