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P2 - RSV-DrugDev
![](/media/z23doqlc/rogermarti.png?width=765&height=450&v=1da6b2d7e70c130)
En bref
Flow Chemistry
HES-SO
VS – Institut Technologies du vivant (Sion), Groupe de recherche Peptide and Protein Technologies
Roger Marti
Répertoire des compétences
janvier 2018 - août 2019
Optimisation de peptides courts doublement agrafés, inhibiteurs de fusion du Virus Respiratoire Syncytial.
Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with an acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. RSV infection is also a serious problem in elderly adults leading to 5% of total hospitalization. Worldwide, RSV infections cause 34 million of ALRI each year. No vaccine is presently available against RSV, as it appears to be extremely difficult to immunize patients without inducing immunopathological responses, especially in the very young population. Treatment options are limited to a costly prophylactic treatment of at-risk infants with the mAb palivizumab (Synagis), and to controversial therapeutic intervention with the nucleoside analogue ribavirin (Rebetol). Thus, there is a need for a more effective treatment for the at-risk population.
Prof. Origène Nyanguile discovered two novel stapled-peptide leads, peptide 4ca and 4bb, which display nanomolar potency in HEp-2 cells, and are exceptionally robust to proteolytic degradation. Furthermore, he showed that intranasal delivery of peptide 4ca to BALB/c mice decreased significantly RSV infection in the upper and lower respiratory tract.
To bring these compounds as close as possible to drug development Prof. Roger Marti worked on the synthesis and scale-up of important building blocks for the production of these peptide antiviral drugs. His team studied and developed an innovative flow synthesis of the challenging alkylation reaction of oxazolidin-5-one derivatives using the elegant concept of self-regeneration of stereocenters introduced by Professor Seebach. With high control of the stereoselectivity and in yields comparable to the batch synthesis this new approach allows the preparation of multi-gram quantities of alkenyl amino acids. These are used for the preparation of the hydrocarbon-stapled peptides.
Prof. Roger Marti presented these results at the Flow Chemistry Symposium 2021 at ILMAC in Basel. This symposium organized by the Swiss Chemical Society focused on recent application flow chemistry in academia and industry.