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)
Sources
Abstract
: 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.
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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.
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