Aptamer-conjugated gold nanoparticles enable oligonucleotide delivery into muscle stem cells to promote regeneration of dystrophic muscles.

Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck of current therapeutic strategies for muscular dystrophies, as it precludes the possibility of promoting compensatory regeneration. Here we describe a muscle-targeting delivery platform, based on gold nanoparticles, that enables the release of therapeutic oligonucleotides into MuSCs. We demonstrate that AuNPs conjugation to an aptamer against α7/β1 integrin dimers directs either local or systemic delivery of microRNA-206 to MuSCs, thereby promoting muscle regeneration and improving muscle functionality, in a mouse model of Duchenne Muscular Dystrophy.

Palladium-Catalyzed PIDA-Mediated δ-C(sp )-H Acetoxylation of Amino Acid Derivatives: Overriding Competitive Intramolecular Amination.

The selective δ-C(sp )-H acetoxylation of N-(SO Py)-protected amino acid derivatives has been accomplished by using palladium-catalysis and PhI(OAc) (PIDA) as both terminal oxidant and acetoxy source. The distinct structural and electronic features of the SO Py compared to more traditional carbonyl-based directing groups is essential to override the otherwise more favourable competitive intramolecular C-H amination. The δ-site selectivity predominates over traditionally more favorable 5-membered cyclopalladation at competitive γ-CH .

Remote -C-H functionalization medium-sized cyclopalladation.

Compared to the tremendous progress made in directed -C-H functionalization five- or six-membered cyclopalladation, protocols with the ability to selectively activate more remote C-H bonds through the intermediacy of larger, less favorable, seven- or eight-membered metalacycles are particularly challenging and remain rare. However, such a strategy would provide new retrosynthetic opportunities for generating structural diversity and complexity. Intense recent research based on the use of either mono-anionic bidentate or monodentate directing groups is characterizing this approach as an increasingly viable tool for selective C-C and C-X bond-forming reactions.

Access to Benzazepinones by Pd-Catalyzed Remote C-H Carbonylation of γ-Arylpropylamine Derivatives.

A general method for the construction of seven-membered rings through Pd-catalyzed C(sp)-H carbonylation at the remote ε-position of γ-arylpropylamine derivatives, including chiral α-amino acids, has been developed using Mo(CO) as the CO source, furnishing richly functionalized benzo[ c]azepin-1-one derivatives. The readily removable N-SOPy protecting/directing group provides high levels of chemo-, regio- and diastereoselectivity. Furthermore, this method is amenable to the postsynthetic modification of complex molecules such as small peptides.