Synthesis of New-to-Nature Atropopeptides by SNAr Macrocyclization for Medicinal Chemistry

Información del proyecto

RiPP-SNAr

Identificador del acuerdo de subvención: 101272210

DOI

10.3030/101272210

Fecha de la firma de la CE 25 Marzo 2026

Fecha de inicio 1 Junio 2026

Fecha de finalización 31 Mayo 2028

Financiado con arreglo a

• Marie Skłodowska-Curie Actions (MSCA)

Coste total

Sin datos

Aportación de la UE

€ 191 918,16

Coordinado por

USTAV ORGANICKE CHEMIE A BIOCHEMIE, AV CR, V.V.I.
Czechia

Objetivo

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large and diverse class of natural products that are fundamental to current drug discovery and development. Most of these peptides contain at least one macrocycle and many bear a stereogenic axis on a tryptophan motif, giving rise to atropisomeric macrocyclic peptides. Atropisomers are intrinsically non-planar, bearing shapes that often minimize the entropic penalty upon their binding to biological receptors, often enhancing potency, selectivity or metabolic stability. Nonetheless, drug discovery efforts have been hampered by lack of synthesis methods toward these peptidic atropisomeric molecules. For instance, there is currently no method for peptide macrocyclization toward C–N atropopeptides directly carried out on the indole of tryptophan. Accordingly, in RIPP-SNAr I will develop the first examples of such peptide macrocyclizations, taking advantage of catalytic nucleophilic aromatic substitution (SNAr). The main advantages are: 1) easy access to starting materials; 2) high modularity allowing for incorporation of structural diversity and 3) several possibilities for controlling atroposelective and atropodiastereodivergency. RIPP-SNAr will therefore provide more sustainable organic synthesis and, because new molecules will be tested biologically, may lead to new anticancer or antibacterial entities. My previous experience in synthesis and medicinal chemistry, acquired as PhD student in the United States, will be relevant to the realization of the project; the hallmark of RIPP-SNAr is the symbiosis between my previous experience in synthesis and medicinal chemistry with the experience in stereoselective catalysis from the host group, inserted at IOCB Prague with its long tradition on such interdisciplinary research. This fellowship will ensure that I become a strong candidate for a leadership position in the pharmaceutical industrial sector.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas
• ciencias naturales › ciencias biológicas › ciencias biológicas del comportamiento › etología › interacción biológica
• ciencias naturales › ciencias químicas › catálisis

Palabras clave

• macrocyclic peptides

Programa(s)

• HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) PROGRAMA PRINCIPAL
  

Tema(s)

• HORIZON-MSCA-2025-PF-01-01 - MSCA Postdoctoral Fellowships 2025
  

Régimen de financiación

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

Convocatoria de propuestas

HORIZON-MSCA-2025-PF

Coordinador

USTAV ORGANICKE CHEMIE A BIOCHEMIE, AV CR, V.V.I.

• Aportación neta de la UEn: € 191 918,16
• Dirección: FLEMINGOVO NAM. 542/2 ; 166 10 PRAHA 6 ; Chequia
• Región: Česko › Praha › Hlavní město Praha
• Tipo de actividad: Research Organisations
• Coste total: Sin datos