The Synthesis Of Guanidine Rich Cell-penetrating Peptides

Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate cellmembranes. Due to their capability to deliver various biologically active cargoes includingproteins, nanoparticles and oligonucleotides into cells, CPPs have been widely used in thestudy of protein function and drug design. However, the currently existing CPPs cannotsatisfy the requirements for further applications in the study of biology and pharmacy interms of the transduction, cytotoxicity and protease resistance. Therefore, it is vitallyimportant and necessary to focus on the design and synthesis for new types of CPPs.The main contents are as follows:1) The first part of this thesis focuses on how I prepared arginine-rich CPPs,including:(1)4types of non-targeting CPPs;(2) CPPs specifical for folate receptors;(3)CPPs specifical for cathepsins. My work has successfully established highly efficientroutes for solid phase peptide synthesis (SPPS) as well as accumulated the practicalexperience for the synthesis of oligomeric α-aminoxy peptides.2) In the second part, new CPPs based on α-aminoxy acids were designed andprepared.(1) Two classes of CPPs rich in α-aminoxy acids were designed based on theprevious research on the influence factors of CPPs including guanidinium groups andamphiphilicity.(2) Suitable synthesis routes were selected to prepare the CPPs.(3) CPPswere synthesized via both solution phase peptide synthesis and SPPS. In a word, from mywork described above, a novel way of the synthesis of hybrid α-aminoxy peptides waswell established for future applications.