Branched peptides as bioactive molecules for drug design

Abstract

Peptides are regarded as good candidates for new biotherapeutics in medicine. Several peptides have already completed clinical development, with more than 60 peptide‐based drugs already on the market, and a further 500 derivatives currently in developmental stages. Branched peptides are an emerging class of synthetic molecules being assessed for drug development. Here, we review possible clinical uses of branched peptides, considering major features such as stability, half‐life, toxicity, and efficacy compared to monomeric peptides, biodistribution, as well as modifications, encapsulation, and conjugation to improve delivery or bypass drug resistance. We focus in particular on the use of branched peptides in oncology and infectious diseases.

An antimicrobial molecule mitigates signs of sepsis in vivo and eradicates infections from lung tissue

“…[30][31][32] However, stability depends on the state of ramification. [30][31][32] However, stability depends on the state of ramification.…”

“…The branched structure of peptides increases their stability to protease degradation. [30][31][32] However, stability depends on the state of ramification. The stability of SET-M33DIM and SET-M33 in serum was compared ( Table 2).…”

“…[23][24][25][26][27][28] It is a non-natural cationic peptide built in tetra-branched form. [30][31][32] It has shown efficacy against a number of Gram-negative multidrug-resistant clinical isolates. [30][31][32] It has shown efficacy against a number of Gram-negative multidrug-resistant clinical isolates.…”

“…29 This structure makes the molecule more resistant to degradation in biological fluids. [30][31][32] It has shown efficacy against a number of Gram-negative multidrug-resistant clinical isolates. 23,26,28 Its mechanism of action is based on binding to LPS and disruption of bacterial membranes.…”

NMR Study of the Secondary Structure and Biopharmaceutical Formulation of an Active Branched Antimicrobial Peptide

“…The synthetic antimicrobial peptide SET-M33 is being developed as a possible new candidate for the development of a new antibacterial drug [1]. Synthesized in branched form with four copies of the same peptide sequence (KKIRVRLSA) on a three-lysine core (Figure 1), it is more resistant to proteases and more suitable for clinical applications than its linear analogues [2,3,4,5]. SET-M33 shows strong antimicrobial activity against several multi-resistant Gram-negative bacteria, including clinical isolates of Pseudomonas aeruginosa , Klebsiella pneumoniae , Acinetobacter baumanii and some enterobacteriaceae [6,7].…”