Job Description

We are offerinf a Post-Doctoral position in Chemistry/Chemical Biology
CY Cergy Paris Université – BioCIS Laboratory

Topic: Design, synthesis and evaluation of fluorinated non-canonical peptides targeting Cathepsin D

Dead line for application : 30/11/2025

BioCIS Laboratory / Chemical Biology Team UMR 8076
CY Cergy Paris University
5 mail Gay-Lussac, Neuville-sur-Oise, 95000 Cergy-Pontoise France
https://biocis.cyu.fr/
Post-Doctoral Position Available
Title: Design, synthesis and evaluation of fluorinated non-canonical peptides targeting Cathepsin D
Context and Project Objectives: Cathepsin D (CD) is one of the most abundant lysosomal protein responsible for
the disposal of exhausted biomolecules.1 Significantly, CD deregulation can contribute to several human diseases,
such as acute kidney injury, Huntington’s, Parkinson’s disease, Alzheimer’s disease (AD), and pancreatitis.2
Moreover, CD imbalance plays an important role in malignant tumors. Increased extracellular levels of CD were
observed in breast, ovarian, colorectal, prostate, and bladder cancer.3 Therefore CD can be considered as an
important target and potent inhibitors of Cathepsin D would help to precise its role in diseases and could lead to
new therapeutics.4 Very recently, we found out that trifluoromethyl non-canonical peptides derived from
Pepstatin A are selective and very potent CD inhibitors.5 As part of the ANR project FLUORAAC “Fluorinated
cyclopropane amino acids: from synthesis to incorporation into peptidic structures for biological applications”
bringing together the teams of Pr. Philippe Jubault and Dr Vincent Tognetti (CARMEN institute, UMR 6064,
Rouen), DR. Florine Cavelier (IBMM, UMR 5247, Montpellier) and Prof. Julien Pytkowicz (BioCIS Laboratory, UMR
8076, Cergy-Pontoise), this task plans to incorporate fluorinated cyclopropane amino acids in the N-terminal part
of Pepstatin A scaffold and test the resulting analogues as CD inhibitors. The mains objectives are:

• Synthesis (SPPS) and characterization of fluorinated Pepstatin A analogues
• Conformational studies and molecular docking experiments on a series of aspartic proteases
• Fluorescence and NMR-based biological evaluation of inhibitors activity
  Candidate’s Requirements: We are looking for a highly motivated chemist ready to work at the interface of
  chemistry and biology and to actively collaborate and interact with all consortium partners. Applicants should
  hold a PhD in Chemistry or Chemical Biology. Experience in manual or automated solid-phase peptide synthesis
  (SPPS) and molecular docking is highly desirable.
  Application Deadline: 30/11/2025
  Starting date: January 2026 (12 months fellowship), average monthly salary 2750€
  To apply: send a CV a cover letter and the name of your current or more recent supervisor at julien.pytkowicz@cyu.fr
  References:
  [1] Yadati, T.; Houben, T.; Bitorina, A.; Shiri-Sverdlov, R. “The Ins and Outs of Cathepsins: Physiological Function and Role in Disease
  Management” Cells 2020, 9, 1679. 10.3390/cells9071679
  [2] Benes, P.; Vetvicka, V.; Fusek, M. “Cathepsin D-Many Functions of One Aspartic Protease” Crit. Rev. Oncol. Hematol. 2008, 68, 12.
  10.1016/j.critrevonc.2008.02.008
  [3] Pranjol, Z. I. M.; Gutowski, N.; Hannemann, M.; Whatmore, J. “The Potential Role of the Proteases Cathepsin D and Cathepsin L in the
  Progression and Metastasis of Epithelial Ovarian Cancer” Biomolecules 2015, 5, 3260. 10.3390/biom5043260
  [4] Dash, C.; Kulkarni, A.; Dunn, B.; Rao, M. “Aspartic Proteases Inhibitors: Implications in Drug Development” Crit. Rev. Biochem. Mol. Biol.
  2003, 38, 89. 10.1080/713609213
  [5] Terzani, F.; Belhattab, S.; Le Guern, A.; Guitot, K.; Monasson, O.; Zanato, C.; Chelain, E.; Leroy-Dudal, J.; Pytkowicz, J. “Synthesis and
  Biological Evaluation of Selective Pepstatin Based Trifluoromethylated Inhibitors of Cathepsin D” Eur. J. Med. Chem. 2024, 267.
  https://doi.org/10.1016/j.ejmech.2024.116178