{"id":51941,"date":"2026-06-17T10:01:54","date_gmt":"2026-06-17T08:01:54","guid":{"rendered":"https:\/\/www.bricbordeaux.com\/event\/thesis-defense-by-mathieu-bourgeais-team-2-bric-cbmn\/"},"modified":"2026-06-24T14:55:13","modified_gmt":"2026-06-24T12:55:13","slug":"thesis-defense-by-mathieu-bourgeais-team-2-bric-cbmn","status":"publish","type":"tribe_events","link":"https:\/\/www.bricbordeaux.com\/en\/event\/thesis-defense-by-mathieu-bourgeais-team-2-bric-cbmn\/","title":{"rendered":"Thesis Defense by Mathieu Bourgeais, Team 2 BRIC & CBMN"},"content":{"rendered":"

Organic Chemistry Thesis Defense: Mathieu Bourgeais, team 2.1<\/strong><\/p>\n

Thesis Title:<\/strong><\/p>\n

Synthesis and Evaluation of Peptide Compounds for the Targeted Degradation of Oncoproteins (french presentation)<\/em><\/p>\n

Thesis advisors:<\/strong><\/p>\n

Abdel-Majid Khatib (BRIC team 2.1) et Gilles Guichard (IECB, CBMN, UMR 5248)<\/p>\n

Date and time of the defense:<\/strong><\/p>\n

June 25, 2026, 9 a.m.<\/p>\n

 <\/p>\n

Location:<\/strong><\/p>\n

Conference room IECB, 2 Rue Robert Escarpit, 33600 Pessac<\/p>\n

Video conference link:<\/strong><\/p>\n

https:\/\/sanofi.zoom.us\/j\/99771203256?pwd=mNK7Iih0btybyAtw0oALnn3dA91D49.1&from=addon<\/a><\/p>\n

Abstract:<\/strong><\/p>\n

This thesis focuses on the design, synthesis, and evaluation of innovative peptide and peptidomimetic compounds intended for the modulation and targeted degradation of oncoproteins. Due to their selectivity and modularity, peptides serve as ideal platforms for targeting hard-to-reach protein-protein interfaces and for exploiting endogenous cellular degradation mechanisms. In this context, two main targets were explored: hDM2, for its E3 ligase activity and its interaction with the tumor suppressor p53, and furin, a proprotein convertase involved in tumor progression. <\/p>\n

In the first phase, constrained ligands mimicking the natural p53 helix were developed as peptide-foldamer hybrids incorporating oligourea segments and macrocyclization patterns derived from structures co-crystallized with hDM2. The exploitation of new cyclization opportunities that stabilize the original alpha-helix\u2014notably through the introduction of cysteines and a mercaptoprolin residue\u2014enabled the stiffening of compounds exhibiting high affinity for hDM2\/hDMX. Careful sequence tuning also revealed that polycationic segments induced p53-independent cytotoxicity, whereas macrocyclic peptide-foldamer hybrids with a net neutral charge restored p53\u2019s antitumor activity in p53wt cancer cells. These optimized ligands thus constitute high-affinity, stable, and permeable modules suitable for subsequent integration into architectures that utilize hDM2 as a target or E3 ligase in the development of PROTAC-type peptidomimetic degraders. <\/p>\n

In a second phase, a robust synthetic route for furin peptide inhibitors was established, enabling the development of analogs active against the recombinant enzyme and in cellular environments. These ligands were then used as a basis for exploring targeted degradation strategies, including hydrophobic tagging, PROTACs targeting the Cereblon or von Hippel-Lindau E3 ligases, and LYTACs targeting internalizing receptors. The results highlight the potential of these approaches while underscoring the constraints imposed by furin\u2019s membrane localization and luminal orientation, which limit the efficacy of certain degradation modalities. <\/p>\n

Taken together, these studies demonstrate that peptidomimetic engineering, combined with macrocyclization strategies, represents a promising approach for generating new bifunctional tools capable of selectively degrading oncoproteins. These advances open up new possibilities for the development of next-generation degraders targeting both intracellular and extracellular targets, demonstrating that such architectures can be rationally optimized to ensure high affinity, increased stability, and the ability to direct proteins to proteasomal or lysosomal degradation pathways. <\/p>\n

 <\/p>\nNotice of Thesis Defense<\/a>\n","protected":false},"excerpt":{"rendered":"

Organic Chemistry Thesis Defense: Mathieu Bourgeais, team 2.1 Thesis Title: Synthesis and Evaluation of Peptide Compounds for the Targeted Degradation of Oncoproteins (french presentation) Thesis advisors: Abdel-Majid Khatib (BRIC team 2.1) et Gilles Guichard (IECB, CBMN, UMR 5248) Date and time of the defense: June…<\/p>\n","protected":false},"author":3,"featured_media":51935,"template":"","meta":{"_tribe_events_status":"","_tribe_events_status_reason":"","footnotes":""},"tags":[],"tribe_events_cat":[91,93,92],"class_list":["post-51941","tribe_events","type-tribe_events","status-publish","has-post-thumbnail","hentry","tribe_events_cat-meetings-en","tribe_events_cat-seminars-en","tribe_events_cat-thesis-defenses-en","cat_meetings-en","cat_seminars-en","cat_thesis-defenses-en"],"_links":{"self":[{"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/tribe_events\/51941","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/tribe_events"}],"about":[{"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/types\/tribe_events"}],"author":[{"embeddable":true,"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/users\/3"}],"version-history":[{"count":3,"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/tribe_events\/51941\/revisions"}],"predecessor-version":[{"id":51997,"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/tribe_events\/51941\/revisions\/51997"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/media\/51935"}],"wp:attachment":[{"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/media?parent=51941"}],"wp:term":[{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/tags?post=51941"},{"taxonomy":"tribe_events_cat","embeddable":true,"href":"https:\/\/www.bricbordeaux.com\/en\/wp-json\/wp\/v2\/tribe_events_cat?post=51941"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}