UE Synthesis of Biomolecules

CHI931 – Synthesis of Biomolecules          
Contact: Pr Eric Defrancq, eric.defrancq@univ-grenoble-alpes.fr
Language of teaching: English
Master program including this course: M2 CLS and M2 Organic Synthesis    
Teaching period: M2 Fall semester (September to December)
Credits: 3 ECTS
Prerequisites: Organic chemistry, heterocyclic chemistry, peptide and carbohydrate synthesis
Course outline: This course describes synthetic approaches and methods for: the preparation of library of small-molecules, the assembly of peptide and analogues, DNA oligonucleotides and conjugates, oligo- and polysaccharides.
Format of the course: 20h of lectures
Format of exams: Ongoing assessment and final written exam (at the end of December) 
Skills: Chemical methods for synthesis and ligations of complex biomolecules (peptides, oligonucleotides and carbohydrates), Combinatorial chemistry: principles/techniques/applications.
Details: 
A.    Peptides and protein engineering (5 lessons)
I.    Peptide and protein structures
II.    Synthetic strategies (SPPS, fragment synthesis, native ligation)
III.    Click Chemistry: the different reactions
IV.    Multiple chemoselective ligations
V.    Installing bioorthogonal functionality into target biomolecules
VI.    In vivo click chemistry

B.    Oligo- and polysaccharides synthesis (3 lessons)
I.    Introduction, reminder structure function,
II.    Synthetic strategies, protection/deprotection, activation methods
III.    1,2-cis and 1,2-trans glycosylations (orthogonal strategies, chemoselective and iterative), programmable synthesis, Mitsunobu, phase transfer catalysis
IV.    Combinatorial, supported, automatized and enzymatic glycosylations
V.    Synthesis of glycoconjugates (N- and O-glycopeptides), conjugation methods and chemoselective ligations
    C.    Combinatorial chemistry (3 lessons)
I.    Drug Discovery
II.    Synthetic strategies (combinatorial vs parallel synthesis; solid vs supported synthesis)
III.    Dynamic Combinatorial Chemistry / Target guided synthesis

D.    DNA oligonucleotides (2 lessons)
I.    Strategies for their synthesis
II.    Preparation of Oligonucleotides Conjugates through chemoselective ligations

Organic chemistry, heterocyclic chemistry, peptide and carbohydrate synthesis