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PolExGene meeting december, 17-18 2007 Ghent. CNRS Montpellier (France), Partner 10 Max Mousseron Institute of Biomolecules Pr. Jean Martinez Dr. Muriel Amblard Dr. Gilles Subra Dr. Jean-Alain Fehrentz Luc Brunel. WP 2 : Synthesis of Selected CPP. WP 3 : Synthesis of Selected CIP.
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PolExGene meeting december, 17-18 2007 Ghent CNRS Montpellier (France), Partner 10 Max Mousseron Institute of Biomolecules Pr. Jean Martinez Dr. Muriel Amblard Dr. Gilles Subra Dr. Jean-Alain Fehrentz Luc Brunel WP 2 : Synthesis of Selected CPP WP 3 : Synthesis of Selected CIP
Cell Penetrating Peptide Synthesis Polyarginine-based peptides Part n° Biotin-(Arg)8-NH2 Biotin-RRRRRRRR-NH2 JMV3674 8 (nov-07)
KALA Translocating Peptide Dr Jani Räty (Part 8 nov-07) KALA peptide - 30 amino acid synthetic peptide, cationic amphipathic peptide - enhances gene delivery Biotine-KALA Biotine-WEAKLAKALAKALAKHLAKALAKALKACEA JMV3690
Cell Interacting Peptide Synthesis RGD-based peptides (avb3 integrin) Partn n° cyclo[Arg-Gly-Asp-(D)Phe-Lysw](H-Cys-Gly-Gly-) JMV3619 1, oct-2007 Integrin: Cell surface receptor that mediates adhesion between cells and extracellular matrix
Needs of PolExGene Partners CPP and CIP Type (Tat, Arg, penetratin, others?) Other specific CIPs ? Fonctionnalisation?
Needs of PolExGene Partners Nter Cys peptides for maleimide ligation or SS bond Ac-Cys-RQIKIWFQNRRMKWKK-OH Ac-Cys-GRKKRRQRRRPPQ-OH Rem: Cys can be repaced by simpler thiol containg group Ac-Cys-RRRRRRRR-OH Cter Cys peptides for maleimide ligation or SS bond Ac-RQIKIWFQNRRMKWKK-Cys-OH Ac-GRKKRRQRRRPPQ-Cys-OH Ac-RRRRRRRR-Cys-OH
Perspectives • Modified CPP Lead CPP (Penetratin, Tat or polyarginine) Bioavailability : synthesis of lead analogues like : D-peptides beta-peptides Peptoids • Selection of CIP Specific sequences for specific receptors: other than RGD?