TY - JOUR
T1 - Flow and Microwave-Assisted Synthesis of N-(Triethylene glycol)glycine Oligomers and Their Remarkable Cellular Transporter Activities
AU - Jong, ThingSoon
AU - Pérez-López, Ana M
AU - Johansson, Emma M V
AU - Lilienkampf, Annamaria
AU - Bradley, Mark
N1 - 09/07/2015
PY - 2015/7/23
Y1 - 2015/7/23
N2 - Peptidomimetics, such as oligo-N-alkylglycines (peptoids), are attractive alternatives to traditional cationic cell-penetrating peptides (such as R9) due to their robust proteolytic stability and reduced cellular toxicity. Here, monomeric N-alkylglycines, incorporating amino-functionalized hexyl or triethylene glycol (TEG) side chains, were synthesized via a three-step continuous-flow reaction sequence, giving the monomers N-Fmoc-(6-Boc-aminohexyl)glycine and N-Fmoc-((2-(2-Boc-aminoethoxy)ethoxy)ethyl)glycine in 49% and 41% overall yields, respectively. These were converted into oligomers (5, 7, and 9-mers) using an Fmoc-based solid-phase protocol and evaluated as cellular transporters. Hybrid oligomers, constructed of alternating units of the aminohexyl and amino-TEG monomers, were non-cytotoxic and exhibited remarkable cellular uptake activity compared to the analogous fully TEG or lysine-like compounds.
AB - Peptidomimetics, such as oligo-N-alkylglycines (peptoids), are attractive alternatives to traditional cationic cell-penetrating peptides (such as R9) due to their robust proteolytic stability and reduced cellular toxicity. Here, monomeric N-alkylglycines, incorporating amino-functionalized hexyl or triethylene glycol (TEG) side chains, were synthesized via a three-step continuous-flow reaction sequence, giving the monomers N-Fmoc-(6-Boc-aminohexyl)glycine and N-Fmoc-((2-(2-Boc-aminoethoxy)ethoxy)ethyl)glycine in 49% and 41% overall yields, respectively. These were converted into oligomers (5, 7, and 9-mers) using an Fmoc-based solid-phase protocol and evaluated as cellular transporters. Hybrid oligomers, constructed of alternating units of the aminohexyl and amino-TEG monomers, were non-cytotoxic and exhibited remarkable cellular uptake activity compared to the analogous fully TEG or lysine-like compounds.
U2 - 10.1021/acs.bioconjchem.5b00307
DO - 10.1021/acs.bioconjchem.5b00307
M3 - Article
C2 - 26155805
SN - 1043-1802
JO - Bioconjugate chemistry
JF - Bioconjugate chemistry
ER -