Synthesis of Peptoids Containing Multiple Nhtrp and Ntrp Residues: A Comparative Study of Resin, Cleavage Conditions and Submonomer Protection.

Published on Apr 29, 2020in Frontiers in chemistry3.693
· DOI :10.3389/FCHEM.2020.00370
Abdullah Lone1
Estimated H-index: 1
(RU: Roskilde University),
Anis Arnous1
Estimated H-index: 1
(RU: Roskilde University)
+ 2 AuthorsHåvard Jenssen40
Estimated H-index: 40
(RU: Roskilde University)
: Peptoids hold status as peptide-mimetics with versatile biological applications due to their proteolytic stability and structural diversity. Among those that have been studied in different biological systems, are peptoids with dominant balanced hydrophobic and charge distribution along the backbone. Tryptophan is an important amino acid found in many biologically active peptides. Tryptophan-like side chains in peptoids allow H-bonding, which is absent from the parent backbone, due to the unique indole ring. Furthermore, the rigid hydrophobic core and flat aromatic system influence the positioning in the hydrocarbon core and allows accommodating tryptophan-like side chains into the interfacial regions of bacterial membranes and causing bacterial membrane damage. Incorporating multiple tryptophan-like side chains in peptoids can be tricky and there is a lack of suitable, synthetic routes established. In this paper, we investigate the synthesis of peptoids rich in Nhtrp and Ntrp residues using different resins, cleavage conditions, and unprotected as well as tert-butyloxycarbonyl-protected amines suitable for automated solid-phase submonomer peptoid synthesis protocols.
Figures & Tables
📖 Papers frequently viewed together
15 Citations
7 Citations
15 Citations
#1Paola Saporito (RU: Roskilde University)H-Index: 3
#2Mojsoska Biljana (RU: Roskilde University)H-Index: 1
Last. Håvard Jenssen (RU: Roskilde University)H-Index: 40
view all 4 authors...
: Escherichia coli is the main etiological agent of urinary trait infections, able to form biofilms in indwelling devices, resulting in chronic infections which are refractory to antibiotics treatment. In this study, we investigated the antimicrobial and anti-biofilm properties exerted against E. coli ATCC 25922, by a set of peptoids and peptides modeled upon the peptide GN-2, previously reported as a valid antimicrobial agent. The putative antimicrobials were designed to evaluate the effect of ...
5 CitationsSource
#1Michelle Vang Mouritzen (RU: Roskilde University)H-Index: 4
#2Håvard Jenssen (RU: Roskilde University)H-Index: 40
Cell migration is an important process that influences many aspects of health, such as wound healing and cancer, and it is, therefore, crucial for developing methods to study the migration. The scratch assay has long been the most common in vitro method to test compounds with anti- and pro-migration properties because of its low cost and simple procedure. However, an often-reported problem of the assay is the accumulation of cells across the edge of the scratch. Furthermore, to obtain data from ...
9 CitationsSource
#1Michela Furlan (UniTS: University of Trieste)H-Index: 7
#2Umberto Rosani (UNIPD: University of Padua)H-Index: 13
Last. Marco Scocchi (UniTS: University of Trieste)H-Index: 37
view all 9 authors...
: Cathelicidins are an important family of antimicrobial peptide effectors of innate immunity in vertebrates. Two members of this group, CATH-1 and CATH-2, have been identified and characterized in teleosts (ray-finned fish). In this study, we investigated the expression of these genes in different tissues of rainbow trout challenged with 4 different inactivated pathogens. By using qPCR, we detected a strong induction of both cath-1 and cath-2 genes within 24 hours after intraperitoneal inoculat...
13 CitationsSource
#1Michelle Vang Mouritzen (RU: Roskilde University)H-Index: 4
#2Sali Abourayale (RU: Roskilde University)H-Index: 1
Last. Håvard Jenssen (RU: Roskilde University)H-Index: 40
view all 8 authors...
The work was funded by the Danish Council for Independent Research, Technology and Production, grant 4005‐00029; Strategic Project POCI‐01‐0145‐FEDER‐007440 funded by FEDER through Operational Programme Competitiveness Factors, the European Foundation for the Study of Diabetes (Novartis European Research Programme in Microvascular Complications of Diabetes), and FCT; and Pepper grant P30 AG028718 and NIGMS‐NIH P20GM109096 to EC.
8 CitationsSource
#1Athina Andrea (RU: Roskilde University)H-Index: 3
#2Natalia Molchanova (RU: Roskilde University)H-Index: 7
Last. Håvard JenssenH-Index: 40
view all 3 authors...
Bacterial biofilms pose a major threat to public health, as they are associated with at least two thirds of all infections. They are highly resilient and render conventional antibiotics inefficient. As a part of the innate immune system, antimicrobial peptides have drawn attention within the last decades, as some of them are able to eradicate biofilms at sub-minimum inhibitory concentration (MIC) levels. However, peptides possess a number of disadvantages, such as susceptibility to proteolytic d...
17 CitationsSource
#1Jiyoun Lee (Sungshin Women's University)H-Index: 22
#2Dahyun Kang (Gwangju Institute of Science and Technology)H-Index: 1
Last. Jiwon Seo (Gwangju Institute of Science and Technology)H-Index: 14
view all 7 authors...
Peptoids are peptidomimetic polymers that are resistant to proteolysis and less prone to immune responses; thus, they can provide a practical alternative to peptides. Among the various therapeutic applications that have been explored, cationic amphipathic peptoids have demonstrated broad-spectrum antibacterial activity, including activity towards drug-resistant bacterial strains. While their potency and activity spectrum can be manipulated by sequence variations, bacterial selectivity and system...
20 CitationsSource
#1Natalia Molchanova (UCPH: University of Copenhagen)H-Index: 7
#2Paul R. Hansen (UCPH: University of Copenhagen)H-Index: 25
Last. Henrik Franzyk (UCPH: University of Copenhagen)H-Index: 29
view all 3 authors...
The rapid emergence of multidrug-resistant pathogens has evolved into a global health problem as current treatment options are failing for infections caused by pan-resistant bacteria. Hence, novel antibiotics are in high demand, and for this reason antimicrobial peptides (AMPs) have attracted considerable interest, since they often show broad-spectrum activity, fast killing and high cell selectivity. However, the therapeutic potential of natural AMPs is limited by their short plasma half-life. A...
94 CitationsSource
#1Pooi Yin Chung (International Medical University)H-Index: 1
#2Ramona Khanum (International Medical University)H-Index: 2
Abstract Bacterial resistance to commonly used drugs has become a global health problem, causing increased infection cases and mortality rate. One of the main virulence determinants in many bacterial infections is biofilm formation, which significantly increases bacterial resistance to antibiotics and innate host defence. In the search to address the chronic infections caused by biofilms, antimicrobial peptides (AMP) have been considered as potential alternative agents to conventional antibiotic...
112 CitationsSource
#1Zhejun Wang (UBC: University of British Columbia)H-Index: 28
#2Ya Shen (UBC: University of British Columbia)H-Index: 58
Last. Markus Haapasalo (UBC: University of British Columbia)H-Index: 84
view all 3 authors...
ABSTRACTThe oral cavity is a major entry point for bacteria and other microorganisms. Oral biofilms are formed by mixed communities of microorganisms embedded in an exopolysaccharide matrix. Biofil...
22 CitationsSource
#1Jeremy A. Turkett (MT: Middle Tennessee State University)H-Index: 2
#2Kevin L. Bicker (MT: Middle Tennessee State University)H-Index: 13
Growing prevalence of antibiotic resistant bacterial infections necessitates novel antimicrobials, which could be rapidly identified from combinatorial libraries. We report the use of the peptoid library agar diffusion (PLAD) assay to screen peptoid libraries against the ESKAPE pathogens, including the optimization of assay conditions for each pathogen. Work presented here focuses on the tailoring of combinatorial peptoid library design through a detailed study of how peptoid lipophilicity relat...
9 CitationsSource
Cited By1
#1Nicki Frederiksen (UCPH: University of Copenhagen)H-Index: 2
#2Paul R. Hansen (UCPH: University of Copenhagen)H-Index: 25
Last. Henrik Franzyk (UCPH: University of Copenhagen)H-Index: 29
view all 8 authors...
The influence of hydrophobicity on antibacterial activity versus the effect on the viability of mammalian cells for peptide/peptoid hybrids was examined for oligomers based on the cationic Lys-like peptoid residue combined with each of 28 hydrophobic amino acids in an alternating sequence. Their relative hydrophobicity was correlated to activity against both Gram-negative and Gram-positive species, human red blood cells, and HepG2 cells. This identified hydrophobic side chains that confer potent...