TY - JOUR

T1 - Synthesis of Peptoids Containing MultipleNhtrp andNtrp Residues

T2 - A Comparative Study of Resin, Cleavage Conditions and Submonomer Protection

AU - Lone, Abdullah

AU - Arnous, Anis

AU - Hansen, Paul Robert

AU - Mojsoska, Biljana

AU - Jenssen, Havard

PY - 2020

Y1 - 2020

N2 - 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 inNhtrp andNtrp residues using different resins, cleavage conditions, and unprotected as well astert-butyloxycarbonyl-protected amines suitable for automated solid-phase submonomer peptoid synthesis protocols.

AB - 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 inNhtrp andNtrp residues using different resins, cleavage conditions, and unprotected as well astert-butyloxycarbonyl-protected amines suitable for automated solid-phase submonomer peptoid synthesis protocols.

KW - peptoids

KW - tryptamine

KW - submonomer synthesis

KW - solid phase synthesis

KW - tryptophan

KW - ANTIMICROBIAL PEPTIDES

KW - ANTIBACTERIAL ACTIVITY

KW - TRYPTOPHAN

KW - LACTOFERRICIN

KW - CYTOTOXICITY

KW - OLIGOMERS

KW - ANALOGS

KW - AGENTS

U2 - 10.3389/fchem.2020.00370

DO - 10.3389/fchem.2020.00370

M3 - Journal article

C2 - 32411678

VL - 8

JO - Frontiers in Chemistry

JF - Frontiers in Chemistry

SN - 2296-2646

M1 - 370

ER -