Designer Peptide and Protein Dendrimers: A Cross-Sectional Analysis

Abstract

Dendrimers have attracted immense interest in science and technology due to their unique chemical structure that offers a myriad of opportunities for researchers. Dendritic design allows us to present peptides in a branched three-dimensional fashion that eventually leads to a globular shape, thus mimicking globular proteins. Peptide dendrimers, unlike other classes of dendrimers, have immense applications in biomedical research due to their biological origin. The diversity of potential building blocks and innumerable possibilities for design, along with the fact that the area is relatively underexplored, make peptide dendrimers sought-after candidates for various applications. This review summarizes the stepwise evolution of peptidic dendrimers along with their multifaceted applications in various fields. Further, the introduction of biomacromolecules such as proteins to a dendritic scaffold, resulting in complex macromolecules with discrete molecular weights, is an altogether new addition to the area of organic chemistry. The synthesis of highly complex and fully folded biomacromolecules on a dendritic scaffold requires expertise in synthetic organic chemistry and biology. Presently, there are only a handful of examples of protein dendrimers; we believe that these limited examples will fuel further research in this area.

Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer

“…It was demonstrated that peptide dendrimers have high biocompatibility and are resistant to proteolytic digestion [ 166 , 167 , 168 ]. This resulted in the application of peptide dendrimers for the delivery of drug and gene materials [ 169 ]. An effort was made for delivery of HSP27-siRNA using peptide dendrimers in the treatment of PCa.…”

The Role of Branch Cell Symmetry and Other Critical Nanoscale Design Parameters in the Determination of Dendrimer Encapsulation Properties

“…It is interesting to note, that this protein-type dendrimer category (i.e., Denkewalter type) has received substantially less attention in the literature compared to traditional Tomalia and Newkome type, symmetrical branch cell dendrimers. According to a recent review article by Haridas et al [31], a SciFinder search from 1993 to 2019 reveals only 282 research publications related to asymmetrical branch cell Denkewalter-type dendrimers have appeared in the literature. In contrast, during this same time (i.e., 1990-2019), >50,000 publications have been documented for symmetrical branch cell containing Tomalia-type dendrimers.…”

“…Earlier interest in poly(peptide) type dendrimers was documented largely by Tam et al [44,45] lysine core dendrimers with tetrapeptides and octapeptides were more soluble in water, more stable to proteolysis and less toxic to human cells than their linear polymeric analogs; comparable antimicrobial potency was demonstrated by Jezek et al [46]. However, recent work by Haridas et al [31] exhaustively reviewed the area of peptide/protein dendrimers and has clearly revealed significant new interest in this overlooked area of dendrimer science. More specifically, Urbanczyk-Lipkowska [47] have described the synthesis and evaluation of amphiphilic peptide dendrimer as specific antimicrobials effective against drug-resistant bacteria [48]; whereas, Reymond et al [49,50] reports the structure-activity relationships for a library of single component, well-defined peptide dendrimers, which are equivalent to Lipofectamine L2000 as a transfection vector for siRNA.…”

Amphiphilic peptide dendrimer-based nanovehicles for safe and effective siRNA delivery

“…The success of amphiphilic dendrimer-based delivery systems has encouraged further exploitation of their diversity. Peptide dendrimers are type of dendrimers composed of amino acids in branch fashion and hold great potentials for biomedical applications by virtue of their unique properties such as protein-mimic structural features, good biocompatibility, and high resistance to proteolytic digestion (Bracci et al 2003;Crespo et al 2005;Darbre and Reymond 2006;Sadler and Tam 2002;Sapra et al 2019). Novel-designed amphiphilic dendrimers featuring peptide dendrimers as hydrophilic heads are expected to show suitable flexibility, good safety profile, and protein-like properties; therefore, they are of particular interest for siRNA delivery (Dong et al 2020;Heitz et al 2019;Inoue et al 2008;Malhotra et al 2012).…”