1262886-66-7Relevant academic research and scientific papers
ApoA-I mimetic peptides promote pre-β HDL formation in vivo causing remodeling of HDL and triglyceride accumulation at higher dose
Carballo-Jane, Ester,Chen, Zhu,O'Neill, Edward,Wang, Jun,Burton, Charlotte,Chang, Ching H.,Chen, Xun,Eveland, Suzanne,Frantz-Wattley, Betsy,Gagen, Karen,Hubbard, Brian,Ichetovkin, Marina,Luell, Silvi,Meurer, Roger,Song, Xuelei,Strack, Alison,Langella, Annunziata,Cianetti, Simona,Rech, Francesca,Capit, Elena,Bufali, Simone,Veneziano, Maria,Verdirame, Maria,Bonelli, Fabio,Monteagudo, Edith,Pessi, Antonello,Ingenito, Raffaele,Bianchi, Elisabetta
, p. 8669 - 8678 (2010)
Reverse cholesterol transport promoted by HDL-apoA-I is an important mechanism of protection against atherosclerosis. We have previously identified apoA-I mimetic peptides by synthesizing analogs of the 22 amino acid apoA-I consensus sequence (apoA-Icons) containing non-natural aliphatic amino acids. Here we examined the effect of different aliphatic non-natural amino acids on the structure-activity relationship (SAR) of apoA-I mimetic peptides. These novel apoA-I mimetics, with long hydrocarbon chain (C 5-8) amino acids incorporated in the amphipathic α helix of the apoA-Icons, have the following properties: (i) they stimulate in vitro cholesterol efflux from macrophages via ABCA1; (ii) they associate with HDL and cause formation of pre-β HDL particles when incubated with human and mouse plasma; (iii) they associate with HDL and induce pre-β HDL formation in vivo, with a corresponding increase in ABCA1-dependent cholesterol efflux capacity ex vivo; (iv) at high dose they associate with VLDL and induce hypertriglyceridemia in mice. These results suggest our peptide design confers activities that are potentially anti-atherogenic. However a dosing regimen which maximizes their therapeutic properties while minimizing adverse effects needs to be established.
