A Class of Cationic Triblock Amphiphilic Oligopeptides as Efficient Gene‐Delivery Vectors

Abstract

A new class of triblock oligopeptides, containing arginine for DNA binding, histidine for intracellular buffering, and hydrophobic residues for enhanced cellular uptake has been designed, with each block offering unique functionalities essential for efficient gene delivery. Together, these materials demonstrate strong DNA binding ability, low cytotoxicity, and significantly higher in vivo gene‐transfection efficiency compared to the PEI standard.

Design and Evaluation of Peptide Amphiphiles with Different Hydrophobic Blocks for Simultaneous Delivery of Drugs and Genes

“…These peptides easily self-assembled into cationic core/shell structured nanoparticles having a hydrophobic core and cationic shell, which were capable of inducing efficient transgene expression in various cell lines. [12][13][14][15] In addition, it has also been reported by our laboratory and other groups that simultaneous delivery of anticancer drugs and genes using cationic core/shell structured nanoparticles achieved a synergistic effect, resulting in an increased transgene expression in vitro [16][17][18][19][20] and improved cancer therapy in a mouse breast cancer model. [16] For example, we have synthesized and designed a triblock oligopeptide with sequence of (AF) 6 H 5 K 15 , which self-assembled into cationic core/shell nanoparticles.…”

Self-assembled Structures from Amphiphilic Peptides

“…[1,5] The sequence of amphiphilic peptides is organized into two regions: the hydrophobic and the hydrophilic part. The latter is predominantly occupied by charged and polar amino acids; these are: arginine (R), [6,7] histidine (H), [7,8] lysine (K), [9][10][11][12][13][14][15] aspartic acid (D), [16,17] glutamic acid (E), [11,18] serine (S), threonine (T), asparagine (N), glutamine (Q), and cysteine (C). [13] The design of the hydrophobic part is based on amino acids with neutral and nonpolar side-chains such as glycine (G), [16] alanine (A), [15,19] valine (V), [17,20] leucine (L), [9,17] isoleucine (I), [21] methionine (M), phenylalanine (F), [22,23] tyrosine (Y), and tryptophan (W).…”

“…[13] The design of the hydrophobic part is based on amino acids with neutral and nonpolar side-chains such as glycine (G), [16] alanine (A), [15,19] valine (V), [17,20] leucine (L), [9,17] isoleucine (I), [21] methionine (M), phenylalanine (F), [22,23] tyrosine (Y), and tryptophan (W). [7,[10][11][12][13][14]23] Depending on the hydrophobic to hydrophilic ratio and the sequence, various self-assembled structures can be constructed -as indicated in the associated references for the above amino acids -although the hydrophobicity is moderated by the polar character of the peptide's backbone.…”

Peptides as Promising Non-Viral Vectors for Gene Therapy

“…This was suggested to be due to a better association between the hydrophobic moieties on the vector and the lipid bilayer (Putnam, 2006). Indeed, a certain degree of hydrophobicity is a common feature of many efficient vectors and this was clearly shown in a recent study where a novel triblock peptide, phobic 5 -his 4 -arg 8 , was developed (Seow & Yang, 2009b;Seow et al, 2009). This design featured a block of five hydrophobic residues (tryptophan, phenylalanine or isoleucine, in order of increasing hydrophobicity) for enhanced uptake, a middle block of four histidines for buffering capacity and a third block of arg 8 for DNA binding and membrane penetration.…”