Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Biochim Biophys Acta ; 1661(1): 1-8, 2004 Feb 10.
Article in English | MEDLINE | ID: mdl-14967469

ABSTRACT

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. It is found that vinblastine does not induce interdigitation in lipids with either shorter or longer alkyl chains than DPPC, or having head-groups of different polarity. In addition, it is shown that the presence of cholesterol in the lipid bilayer tends to modulate the phase behavior of the lipid/vinblastine bilayer system. Preliminary studies show that such properties directly affect the encapsulation efficiency and the pharmacokinetics of liposomes.


Subject(s)
Cholesterol/pharmacology , Lipid Bilayers/chemistry , Vinblastine/chemistry , Androstanes/chemistry , Calorimetry, Differential Scanning , Cholesterol/chemistry , Dimyristoylphosphatidylcholine/chemistry , Drug Carriers , Membrane Fluidity , Thermodynamics
2.
J Med Chem ; 45(2): 275-83, 2002 Jan 17.
Article in English | MEDLINE | ID: mdl-11784132

ABSTRACT

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. Replacement of Lys and/or Pro residues with Arg and/or Ala, respectively, results in suppression of EAE. A potent linear altered peptide ligand of the immunodominant sequence MBP(83-99) has been selected for clinical trial (Nat. Med. 2000, 6, 1167, 1176). In the present report, two cyclic analogues, cyclo(91-99)[Ala(96)]MBP(87-99) and cyclo(87-99)[Arg(91), Ala(96)]MBP(87-99) were designed by NMR and molecular modeling data on human MBP(87-99) epitope (Val(87)-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro(99)) and its linear antagonist peptide analogue [Arg(91), Ala(96)]MBP(87-99). These analogues (altered peptide ligands) inhibited EAE in Lewis rats and decreased inflammation in the spinal cord. In addition, the analogue cyclo(87-99)[Arg(91), Ala(96)]MBP(87-99) induced proliferation of human peripheral blood T-cells. These cyclic MBP(87-99) peptide analogues may lead to the design of potent antagonist mimetics for treating MS.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Myelin Basic Protein/chemical synthesis , Peptide Fragments/chemical synthesis , T-Lymphocytes/drug effects , Animals , Cell Division , Encephalomyelitis, Autoimmune, Experimental/pathology , Epitopes , Humans , In Vitro Techniques , Ligands , Magnetic Resonance Spectroscopy , Models, Molecular , Myelin Basic Protein/chemistry , Myelin Basic Protein/pharmacology , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , Rats , Rats, Inbred Lew , Spinal Cord/pathology , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL
...