Tesis doctoral de José Antonio Morales Serna
Several viral envelope glycoprotein oligomers assembled into a viral fusion machine, form a molecular scaffold that brings the viral and target cell membranes into close apposition and allow the subsequent fusion events. The fusion pore formation and its sequential expansion are orchestrated by viral and cellular lipids and proteins. The hiv entry process is understood in some detail at the molecular level. It is coordinated by the hiv envelope glycoprotein complex, a trimer of three gp120 surface glycoproteins, each noncovalently attached to three gp41 ransmembrane glycoprotein subunits.%&/It is know that changes in gsls expression in target membranes can modulate viral fusion and entry. These studies on structure-function relationship of target membrane gsls, the gp120-gp41 and the viral receptors suggest that plasma membrane gsls support hiv-1 entry by stabilizing the intermediate steps in the fusion cascade. These observations, led it to hypothesize that upregulation of gsls metabolites (such as ceramide) and/or modulation of gsls, which preferentially partition in the plasma membrane microdomains, could have a significant influence on hiv-1 entry. %&/Based on these findings, in this work has been developed a strategy to synthesize glycodentritic polymers that bind hiv rgp120 and inhibit hiv-1 entry. To reach this goal, first it was carried out the total synthesis of d-erytrho-sphingosine with high enantioselectivity and diasteroselectivity. Then, an efficient protocol of glycosylation of ceramides employing stannyl derivatives as strategy was developed. Finally, water-soluble hyperbranched glycodendritic polymers for the study of carbohydrate interactions were synthesized. These glycoconjugate consists of boltorn h30 hyperbranched polymers, based on the monomer 2,2-bis(hydroxymethyl)propionic acid, functionalized with naturally occurring -galceramide. The click chemistry permits functional group tolerance during the derivatization of boltorn h30. Their ability to bind hiv-1 rgp 120 was demonstrated using surface plasmon resonance (spr).
Datos académicos de la tesis doctoral «Synthesis of glycolipids and glycodendritic polymers that bind hiv rgp 120«
- Título de la tesis: Synthesis of glycolipids and glycodendritic polymers that bind hiv rgp 120
- Autor: José Antonio Morales Serna
- Universidad: Rovira i virgili
- Fecha de lectura de la tesis: 19/06/2009
Dirección y tribunal
- Director de la tesis
- Sergio Castillon Miranda
- Tribunal
- Presidente del tribunal: Francisco Santoyo gonzález
- Francisco Javier Rojo marcos (vocal)
- María í ngels Serra albet (vocal)
- carmen Ortiz mellet (vocal)