Cell-penetrating peptides having a central hydrophobic domain

摘要

The present invention discloses cell penetrating peptides (CPP or membrane translocating peptide) and their conjugates with cargo molecules. The peptides are useful as drug delivery systems, particularly as delivery vehicles for nucleotide-based therapeutics, such as polynucleotides, oligonucleotides and peptide nucleic acids. A CPPs of the invention provides a balance between good cell entry efficiency and low toxicity and comprises three contiguous domains: the central one being hydrophobic and the flanking ones consisting of arginine and aminohexanoic acid or beta-alanine residues. The hydrophobic domain contains a sequence selected from YQFLI, YRFLI, IQFLI and IRFLI.

主权项

1. A peptide, having a primary sequence structure comprised of at least three domains, having the arrangement:
N-terminus [Domain 1]-[Domain 2]-[Domain 3] C-terminuswherein
the total number of residues in Domains 1-3 combined is no more than 40, the number of R (Arginine) residues in Domains 1 and 3 combined is at least 5, the number of X residues in Domains 1 and 3 combined is at least 1, the number of B residues in Domains 1 and 3 combined is at least 2, wherein X=aminohexanoic acid and B=betaAlanine, Domain 2 comprises a sequence that contains at least 3 of the amino acids Z1Z2FLI [SEQ ID NO:798], where Z1, is Y or I and Z2 is Q or R, and Domain 2 does not contain an N- to C-terminal contiguous primary sequence of ILFQY [SEQ ID NO:799], ILFQ [SEQ ID NO:800] or ILIQ [SEQ ID NO:801].