945259-80-3Relevant academic research and scientific papers
Squalene-derived flexible linkers for bioactive peptides
Jagadish, Bhumasamudram,Sankaranarayanan, Rajesh,Xu, Liping,Richards, Reyniak,Vagner, Josef,Hruby, Victor J.,Gillies, Robert J.,Mash, Eugene A.
, p. 3310 - 3313 (2008/02/08)
A regiochemical and stereochemical mixture of flexible linkers bearing terminal azide functionality was synthesized in two steps from squalene and was used to connect two high affinity NDP-α-MSH ligands or two low affinity MSH(4) ligands. The ligands were N-terminally acylated using N-hydroxysuccinimidoyl 5-hexynoate and were subsequently attached to the linker via copper-catalyzed 'click' 3 + 2 cyclization of the azide and alkyne moieties. In vitro biological evaluations showed that the binding affinity to the human melanocortin 4 receptor was not diminished for most linker-ligand combinations relative to the corresponding parental ligand. Statistical and cooperative binding effects were observed for dimeric constructs containing the low affinity ligand MSH(4), but not for dimeric NDP-α-MSH constructs, presumably due to slow off rates for this high affinity ligand.
