Basic concepts of organic synthesis. Physical methods of characterization of bioactive molecules. Synthesis of peptides in solution and in solid phase. Combinatorial chemistry. Peptide analysis and biological screening. Bioconjugation techniques. Principles and applications of molecular imaging.
Nanoparticles (NP): definition, classification, synthesis and in vitro chemical, chemical-physical and biological characterization. Application of NP in teranostics.
Greg T. Hermanson, Bioconjugate Techniques, Academic Press USA
Ravin Narain, Chemistry of Bioconjugates: Synthesis, Characterization, and Biomedical Applications, John Wiley & Sons
Materials provided by the teacher.
Learning Objectives
Knowledge:
The aim of the course is to provide detailed knowledge of the properties of the main classes of biomolecules and their chemical behavior, including a brief overview on nanotechnology.
Skills:
The student will be able to design a peptide synthesis and libraries of compounds with potential biological activity. In addition the student will recognize in the main biomolecules (peptides and proteins, sugars and polysaccharides, nucleic acids and oligonucleotides) the functional groups suitable for labeling with fluorophores or radionuclide and employable synthesis strategies to express on them functional groups not normally present. Know the main classes of fluorophores and their capabilities for bioconjugation.
Furthermore, the student will acquire expertise on the biofunctionalization of nanoparticles of different nature and on the application of biofunctional nanosystems in different biomedical fields.
Skills acquired at the end of the course:
Ability to choose the best methodological approaches for peptide synthesis and labeling of complex biomolecules in an autonomous and conscious way. Basic knowledge for the design of biofunctional nanomaterials to solve biological problems.
Prerequisites
Courses recommended: General and Inorganic Chemistry, Organic Chemistry.
Teaching Methods
Total hours of the course: 150.
Hours reserved to private study and other individual formative activities: 102
Contact hours for Lectures: 48 hours including 8 hours for laboratory exercises.
Further information
Frequency of lectures and exercises: Highly recommended
Teaching tools: Power point presentations of the lectures, Moodle program.
Type of Assessment
The examination includes an oral text to ascertain the understanding and ability to explain in a clear and appropriate way the topics of the course. It will also be evaluated for their ability to apply their knowledge to some practical problems (synthesis design of biologically active molecules or transformation of functional groups present on biomolecules for labeling with the appropriate agents).
Course program
Introduction to the course. Importance of laboratory synthesis of bioactive organic compounds.
Basic concepts of organic synthesis: main synthetic, isolation and purification strategies, functional groups, protecting groups, basic reactions, atom economy, click chemistry.
General features of amino acids and peptides. Examples of bioactive peptides. Protecting groups in peptide synthesis. Peptide bond formation: activation and coupling methods. Synthesis in solution and in solid phase. Conformational studies: CD, NMR, IR methodologies to define the secondary conformation of the peptide. Combinatorial chemistry applied to peptide libraries. Peptide analysis. Preparation of libraries of organic compounds and biological screening methods.
Bioconjugation techniques for the monitoring and study of biomolecules through the formation of covalent bonds with molecules of easy detection and radionuclides. Importance and application of bioconjugation techniques in the disciplines of life sciences.
Analysis of the functional groups available for bioconjugation and synthesis strategies that can be used to express functional groups not normally present in the biomolecules of main interest, peptides and proteins, sugars and polysaccharides, nucleic acids and oligonucleotides.
Properties used for detection: absorption, radioactivity, fluorescence, biotin markers, followed by examination of the main molecules capable of expressing these properties also in light of their availability on the market. Types of fluorophores and applications in bioconjugation: fluorescein, rhodamine, cyanine, coumarins.
Molecular imaging: General principles of Molecular Imaging, main Imaging techniques (MRI, PET, SPECT, CT, fluorescence), Molecular Imaging probes (contrast agents for MRI, PET tracers, SPECT), applications of Molecular Imaging in Oncology , Cardiovascular, Neurological.
Covalent and non-covalent bioconjugation techniques for "Antibody Drug Conjugates" (ADC) and nanoparticles (NP). Definition and classification of NP ("soft", "hard", "hybrid"); outline of synthesis, chemical and chemical-physical characterization of NP and in vitro biological characterization. NP as carriers for drug delivery (anticancer, "gene delivery", vaccines, etc.) and NP with response to stimuli for "smart delivery". Use of NP in molecular and multimodal image (SPION, QD, Gd-NP, functionalised with fluorophores, radionuclides, etc.) Multifunctional NPs. Modification of sugars: glycoconjugates and glyconanotechnology.