The modulation of thermal properties of vinblastine by cholesterol in membrane bilayers.

It has been shown that the partitioning of vinblastine in 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) single and multiple bilayer dispersions induces partial interdigitation of the lipid alkyl chains. Similar behavior has been observed for abietic and ursodeoxycholic acids and may well be generalized for the partitioning of bulky amphoteric molecules, which tend to localize in the vicinity of the polar heads. For the present study, differential scanning calorimetry (DSC) has been employed to investigate the role of lipid molecular characteristics such as the alkyl chain length and the polarity of the head-group, as well as the impact of cholesterol upon vinblastine-induced interdigitation.

Efforts to understand the molecular basis of hypertension through drug:membrane interactions.

Biological membranes play an essential role in the drug action. They constitute the first barrier for drugs to exert their biological action. AT1 antagonists are amphiphilic molecules and are hypothesized to act on AT1 receptor through incorporation (first step) and lateral diffusion through membrane bilayers (second step).

Losartan's molecular basis of interaction with membranes and AT1 receptor.

Physicochemical methods were used to study the thermal and dynamic changes caused by losartan in the membrane bilayers. In addition, molecular modeling was implemented to explore its topography both in membranes and AT(1) receptor. Its incorporation resulted in the modification of thermal profile of dipalmitoyl phosphatidylcholine (DPPC) bilayers in a concentration dependent way up to 20mol% as it is depicted from the combination of differential scanning calorimetry (DSC) and MAS data.

A molecular basis explanation of the dynamic and thermal effects of vinblastine sulfate upon dipalmitoylphosphatidylcholine bilayer membranes.

Differential scanning calorimetry has been employed to study the thermal effects of vinblastine sulfate upon aqueous, single and multiple bilayer dispersions of 1,2-dipalmitoyl-3-sn-phosphatidylcholine (DPPC). The calorimetric results summarized to an increase in the gel to liquid-crystalline phase transition enthalpy and the abolishment of the L(beta)' (gel phase) to P(beta)' (ripple phase) pretransition for the uni- and multilamellar dispersions, as well as an increase in the transition temperature T(m) and the transition cooperativity for single bilayer DPPC/vinblastine mixed vesicles, are consistent with an induced, partially interdigitated, gel phase. Computational analysis has been successfully applied to clarify the intermolecular effects and verify the feasibility of the proposed interdigitation for the vinblastine sulfate molecules and also for the ursodeoxycholic acid (UDCAH) and bromocylated taxanes, which have been shown to induce an interdigitated gel phase in DPPC bilayers.

Antagonistic effects of human cyclic MBP(87-99) altered peptide ligands in experimental allergic encephalomyelitis and human T-cell proliferation.

The immunodominant myelin basic protein (MBP) peptide comprising residues 87-99 is a self-antigen in multiple sclerosis (MS). In Lewis rats this epitope induces experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, and is a model of MS. Structure-activity studies have shown that Lys(91) and Pro(96) residues are important for encephalitogenicity.