141743-13-7Relevant articles and documents
Peptide/peptoid hybrid oligomers: The influence of hydrophobicity and relative side-chain length on antibacterial activity and cell selectivity
Frederiksen, Nicki,Hansen, Paul R.,Bj?rkling, Fredrik,Franzyk, Henrik
, (2019)
Previous optimisation studies of peptide/peptoid hybrids typically comprise comparison of structurally related analogues displaying different oligomer length and diverse side chains. The present work concerns a systematically constructed series of 16 closely related 12-mer oligomers with an alternating cationic/hydrophobic design, representing a wide range of hydrophobicity and differences in relative side-chain lengths. The aim was to explore and rationalise the structure-activity relationships within a subclass of oligomers displaying variation of three structural features: (i) cationic side-chain length, (ii) hydrophobic side-chain length, and (iii) type of residue that is of a flexible peptoid nature. Increased side-chain length of cationic residues led to reduced hydrophobicity till the side chains became more extended than the aromatic/hydrophobic side chains, at which point hydrophobicity increased slightly. Evaluation of antibacterial activity revealed that analogues with lowest hydrophobicity exhibited reduced activity against E. coli, while oligomers with the shortest cationic side chains were most potent against P. aeruginosa. Thus, membrane-disruptive interaction with P. aeruginosa appears to be promoted by a hydrophobic surface of the oligomers (comprised of the aromatic groups shielding the cationic side chains). Peptidomimetics with short cationic side chains exhibit increased hemolytic properties as well as give rise to decreased HepG2 (hepatoblastoma G2 cell line) cell viability. An optimal hydrophobicity window could be defined by a threshold of minimal hydrophobicity conferring activity toward E. coli and a threshold for maximal hydrophobicity, beyond which cell selectivity was lost.
An Electrochemical Approach to Designer Peptide α-Amides Inspired by α-Amidating Monooxygenase Enzymes
Lin, Yutong,Malins, Lara R.,Malins, Lara R.
supporting information, p. 11811 - 11819 (2021/08/16)
Designer C-terminal peptide amides are accessed in an efficient and epimerization-free approach by pairing an electrochemical oxidative decarboxylation with a tandem hydrolysis/reduction pathway. Resembling Nature's dual enzymatic approach to bioactive primary α-amides, this method delivers secondary and tertiary amides bearing high-value functional motifs, including isotope labels and handles for bioconjugation. The protocol leverages the inherent reactivity of C-terminal carboxylates, is compatible with the vast majority of proteinogenic functional groups, and proceeds in the absence of epimerization, thus addressing major limitations associated with conventional coupling-based approaches. The utility of the method is exemplified through the synthesis of natural product acidiphilamide A via a key diastereoselective reduction, as well as bioactive peptides and associated analogues, including an anti-HIV lead peptide and blockbuster cancer therapeutic leuprolide.
Tuning conformation and properties of peptidomimetic backbones through dual: N / C α-substitution
Kaminker,Kaminker,Gutekunst,Luo,Lee,Niu,Han,Hawker
supporting information, p. 5237 - 5240 (2018/05/28)
We demonstrate that changing the backbone between peptides, peptoids and the underexplored dual N/Cα-substituted peptoids analogues allows for control over the preferred conformation of the intrinsically disordered biomimetic oligomers. The con
