Effect of amphipathic HIV fusion inhibitor peptides on POPC and POPC/cholesterol membrane properties: a molecular simulation study.

T-20 and T-1249 fusion inhibitor peptides were shown to interact with 1-palmitoyl-2-oleyl-phosphatidylcholine (POPC) (liquid disordered, ld) and POPC/cholesterol (1:1) (POPC/Chol) (liquid ordered, lo) bilayers, and they do so to different extents. Although they both possess a tryptophan-rich domain (TRD), T-20 lacks a pocket binding domain (PBD), which is present in T-1249. It has been postulated that the PBD domain enhances FI interaction with HIV gp41 protein and with model membranes.

Behavior of fluorescent cholesterol analogues dehydroergosterol and cholestatrienol in lipid bilayers: a molecular dynamics study.

Molecular dynamics simulations of bilayer systems consisting of varying proportions of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), cholesterol (Chol), and intrinsically fluorescent Chol analogues dehydroergosterol (DHE) or cholestatrienol (CTL) were carried out to study in detail the extent to which these fluorescent probes mimic Chol's behavior (location, orientation, dynamics) in membranes as well as their effect on host bilayer structure and dynamics (namely their ability to induce membrane ordering in comparison with Chol). Control properties of POPC and POPC/Chol bilayers agree well with published experimental and simulation work. Both probes and Chol share similar structural and dynamical properties within the bilayers.

Sensing hydration and behavior of pyrene in POPC and POPC/cholesterol bilayers: a molecular dynamics study.

Molecular dynamics (MD) simulations of bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) with varying amounts of cholesterol (0, 5, 20, and 40mol%) were carried out in the absence and presence of inserted pyrene molecules. Both fluorophore and bilayer parameters were computed, for characterization of probe location and dynamics, as well as its effects on the host bilayer. In agreement with previous studies in fluid disordered bilayers, pyrene prefers to be located in the hydrophobic acyl chain region of POPC bilayers, close to the glycerol group of lipid molecules and causes ordering of the lipid acyl chains.

T-20 and T-1249 HIV fusion inhibitors' structure and conformation in solution: a molecular dynamics study.

Fusion of the HIV envelope with the target cell membrane is a critical step of the HIV entry into the target cell. Several peptides based on the C-region of HIV gp41 have been used in clinical trials as possible HIV fusion inhibitors. Among these are T-1249 and T-20 (also known as enfurvitide).