Biswanath Maity, Hariharan Moorthy and Thimmaiah Govindaraju*,
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引用次数: 0
Abstract
Efficient delivery of bioactive ingredients into cells is a major challenge. Cell-penetrating peptides (CPPs) have emerged as promising vehicles for this purpose. We have developed novel CPPs derived from the flexible and disordered tail extensions of DNA-binding Ku proteins. Ku-P4, the lead CPP identified in this study, is biocompatible and displays high internalization efficacy. Biophysical studies show that the proline residue is crucial for preserving the intrinsically disordered state and biocompatibility. DNA binding studies showed effective DNA condensation to form a positively charged polyplex. The polyplex exhibited effective penetration through the cell membrane and delivered the plasmid DNA inside the cell. These novel CPPs have the potential to enhance the cellular uptake and therapeutic efficacy of peptide-drug or gene conjugates.
将生物活性成分高效地输送到细胞中是一项重大挑战。为此，细胞穿透肽（CPPs）已成为一种很有前景的载体。我们从 DNA 结合 Ku 蛋白的柔性无序尾端延伸部分开发出了新型 CPPs。Ku-P4是本研究中发现的主要CPP，它具有生物相容性，并显示出很高的内化效力。生物物理研究表明，脯氨酸残基对于保持固有无序状态和生物相容性至关重要。DNA 结合研究表明，DNA 能有效缩合，形成带正电荷的多聚体。这种多聚体能有效穿透细胞膜，将质粒 DNA 送入细胞内。这些新型 CPPs 有潜力提高细胞对多肽-药物或基因共轭物的吸收和治疗效果。
期刊介绍：
ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.
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