Noncanonical Amino Acids Dictate Peptide Assembly in Living Cells

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

ConspectusEmulating the structural features or functions of natural systems has been demonstrated as a state-of-the-art strategy to create artificial functional materials. Inspired by assembly and bioactivity proteins, self-assembly peptides into nanostructures represents promising approach for creating biomaterials. Conventional assembled peptide biomaterials are typically formulated in solution delivered pathological sites implementing theranostic objectives. However, this translocation entails switch from formulation conditions physiological environment raises concerns about material performance. In addition, precise efficient accumulation administered at target remains significant challenge, leading potential biosafety issues associated with off-target effects. These limitations significantly hinder progress advanced To address these concerns, past few years have witnessed development situ living new endeavor optimizing biomaterial performance benefiting advances stimuli-responsive reactions regulating noncovalent interactions. refers processes via sites. Due advantages precisely forming well-defined lesions, situ-formed assemblies integrated interesting next-generation biomedical agents.Despite great developing agents, research area still suffers limited toolkit operating under complicated conditions. Considering amino acids being incorporated backbones modified units, an acid is concern. Therefore, our laboratory intensively engaged designing discovering noncanonical (ncAAs) expand manipulating various biological Thus far, we synthesized containing ncAAs 4-aminoproline, 2-nitroimidazole alanine, Se-methionine, sulfated tyrosine, glycosylated serine, which allow us develop acid-responsive, redox-responsive, enzyme-responsive systems. Based on ncAAs, established complex self-sorting assembly, self-amplified dissipative cells optimize peptides. The resulting exhibit morphological adaptability microenvironment, contributes overcoming delivery barriers improvement targeting accumulation. utilizing developed toolkit, further created supramolecular PROTACs, antagonists, probes cancer treatment diagnosis highlight implications usage. Account, summarize journey emphasis mechanism Eventually, also provide forward conceiving prospects challenges clinical translation situ-formulated

Language: Английский

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DNA Nanostructures for Rational Regulation of Cellular Organelles

JACS Au, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

DNA nanotechnology has revolutionized materials science and biomedicine by enabling precise manipulation of matter at the nanoscale. nanostructures (DNs) in particular represent a promising frontier for targeted therapeutics. Engineered DNs offer unprecedented molecular programmability, biocompatibility, structural versatility, making them ideal candidates advanced drug delivery, organelle regulation, cellular function modulation. This Perspective explores emerging role modulating behavior through organelle-targeted interventions. We highlight current advances nuclear, mitochondrial, lysosomal targeting, showcasing applications ranging from gene delivery to cancer For instance, have enabled precision mitochondrial disruption cells, pH modulation enhance silencing, nuclear gene-editing templates. While hold immense promise advancing nanomedicine, outstanding challenges include optimizing biological interactions addressing safety concerns. highlights potential rational control organelles, which could lead novel therapeutic strategies advancement nanomedicines future.

Language: Английский

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Functionalization of Nucleic Acid Molecular Machines under Physiological Conditions: A Review

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

In-situ fabrication of nucleic acid molecular machines in biological environments is desirable for smart theranostic applications. However, given the complex nature environments, integration multiple functional modules into a coordinated machine remains challenging. Recent advances nanotechnology offer solutions to these challenges. Here, we outline design principles acid–based tailored physiological conditions, drawing on recent examples. We review cutting-edge technologies that facilitate their functionalization settings, particularly presynthesis modifications using unnatural bases and postsynthesis via bioorthogonal chemistry noncovalent interactions. discuss advantages limitations suggest future directions overcome existing

Language: Английский

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Synthetic Nanoassemblies for Regulating Organelles: From Molecular Design to Precision Therapeutics

ACS Nano, Journal Year: 2024, Volume and Issue: 18(44), P. 30224 - 30246

Published: Oct. 23, 2024

Each organelle referring to a complex multiorder architecture executes respective biological processes via its distinct spatial organization and internal microenvironment. As the assembly of biomolecules is structural basis living cells, creating synthetic nanoassemblies with specific physicochemical morphological properties in cells interfere or couple natural architectures has attracted great attention precision therapeutics cancers. In this review, we give an overview latest advances for precise regulation, including formation mechanisms, triggering strategies, biomedical applications therapeutics. We summarize emerging material systems, polymers, peptides, deoxyribonucleic acids (DNAs), their intermolecular interactions intercellular nanoassemblies, highlight design principles constructing precursors that assemble into targeting organelles cellular environment. further showcase developed intracellular mitochondria, endoplasmic reticulum, lysosome, Golgi apparatus, nucleus describe underlying mechanisms regulation cancer. Last, essential challenges field prospects future are discussed. This review should facilitate rational organelle-targeting comprehensive recognition by materials contribute deep understanding application

Language: Английский

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Metal Ion-Condensed DNA Nanoparticle Library: Phase Separation and Transition and Antisense Therapy Applications

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(43), P. 59116 - 59127

Published: Oct. 20, 2024

DNA condensation has long been investigated as a fundamental cellular activity and is known to be driven by the mediation of diverse condensing agents. The phase behaviors during are particularly interesting because complicated molecular structure natural nucleotides fundamentally allows electrostatic, coordinate covalent, various other secondary interactions with Recently, metal ion (M

Language: Английский

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