RESUMO
A synthetic route for the preparation of symmetrical and unsymmetrical archaeal tetraether-like analogues has been described. The syntheses are based upon the elaboration of hemimacrocyclic tetraether lipid cores from versatile building blocks followed by simultaneous or sequential introduction of polar head groups. Functionalizations of the tetraether lipids with neutral lactose or phosphatidylcholine polar heads and cationic glycine betaine moieties were envisaged both to increase membrane stability and to exhibit interactions with charged nucleic acids. Additionally, mannose and lactose triantennary clusters designed as multivalent ligands for selective interaction with lectin-type receptors were also efficiently synthesized for active cell/tissue targeting.
Assuntos
Archaea/química , Lipídeos/síntese química , Lipídeos/farmacologia , Archaea/genética , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes , Humanos , Lactose/química , Ligantes , Lipídeos/química , Manose/química , Conformação Molecular , Ácidos Nucleicos/química , Receptores de Superfície Celular/química , Receptores de Superfície Celular/efeitos dos fármacos , EstereoisomerismoRESUMO
Unsymmetrical archaeal tetraether glycolipid analogues 1-2 incorporating a 1,3-disubstituted cyclopentane ring into the bridging chain have been synthesized. The cyclopentane has been introduced with a totally controlled cis configuration, either into the middle of the aliphatic chain or at three methylene groups from the glycerol unit linked to the bulkier disaccharide residue. Freeze-fracture and cryotransmission electron microscopy experiments clearly demonstrated unprecedented glycolipid supramolecular organizations involving two-by-two monolayer associations coupled with interconnection and fusion phenomena. Furthermore, a significant difference in the hydration properties and in the lyotropic liquid crystalline behavior of bipolar lipids 1-2 was found depending on the position of the cyclopentane residue.