Department of Chemistry & School of Sustainable Design and Engineering, University of Prince Edward Island, C1A 4P3, Charlottetown, PEI, Canada.
Biomater Sci. 2017 Oct 24;5(11):2188-2211. doi: 10.1039/c7bm00584a.
Cell penetrating peptides (CPPs), and protein transduction domains (PTDs) of viruses and other natural proteins serve as a template for the development of efficient peptide based gene delivery vectors. PTDs are sequences of acidic or basic amphipathic amino acids, with superior membrane trespassing efficacies. Gene delivery vectors derived from these natural, cationic and cationic amphipathic peptides, however, offer little flexibility in tailoring the physicochemical properties of single chain peptide based systems. Owing to significant advances in the field of peptide chemistry, synthetic mimics of natural peptides are often prepared and have been evaluated for their gene expression, as a function of amino acid functionalities, architecture and net cationic content of peptide chains. Moreover, chimeric single polypeptide chains are prepared by a combination of multiple small natural or synthetic peptides, which imparts distinct physiological properties to peptide based gene delivery therapeutics. In order to obtain multivalency and improve the gene delivery efficacies of low molecular weight cationic peptides, bioactive peptides are often incorporated into a polymeric architecture to obtain novel 'polymer-peptide hybrids' with improved gene delivery efficacies. Peptide modified polymers prepared by physical or chemical modifications exhibit enhanced endosomal escape, stimuli responsive degradation and targeting efficacies, as a function of physicochemical and biological activities of peptides attached onto a polymeric scaffold. The focus of this review is to provide comprehensive and step-wise progress in major natural and synthetic peptides, chimeric polypeptides, and peptide-polymer hybrids for nucleic acid delivery applications.
细胞穿透肽（CPPs）和病毒及其他天然蛋白的蛋白转导结构域（PTDs）可作为开发高效肽基基因传递载体的模板。PTDs 是酸性或碱性两亲性氨基酸的序列，具有优越的膜穿透效率。然而，源自这些天然、阳离子和两性离子肽的基因传递载体在调整单链肽基系统的物理化学性质方面几乎没有灵活性。由于肽化学领域的重大进展，经常制备天然肽的合成模拟物，并评估其基因表达能力，这取决于氨基酸功能、肽链的结构和净阳离子含量。此外，通过组合多个天然或合成小肽来制备嵌合单多肽链，这为基于肽的基因传递治疗剂赋予了独特的生理特性。为了获得多价性并提高低分子量阳离子肽的基因传递效率，生物活性肽经常被整合到聚合物结构中，以获得具有改进的基因传递效率的新型“聚合物-肽杂化物”。通过物理或化学修饰制备的肽修饰聚合物，由于附着在聚合物支架上的肽的物理化学和生物学活性，表现出增强的内涵体逃逸、刺激响应降解和靶向效率。本综述的重点是提供用于核酸传递应用的主要天然和合成肽、嵌合多肽和肽-聚合物杂化物的全面和逐步进展。
