Organic Chemistry Applied to Biology
A.Y. 2024/2025
Learning objectives
This course aims to provide the student with the foundation of organic synthesis and analytical chemistry, useful for the rational design, synthesis and characterization of small molecules endowed with biological activity, with particular relevance in the pharmaceutical sector.
The two main topics draw the student's attention to multi-disciplinary, chemistry-driven approaches to achieve a common goal - due to this, synthetic and analytical disciplines and techniques are often referred to in various contexts (for example, the use of NMR spectroscopy in the generation of molecular target models, and in the evaluation of target-ligand interactions).
The two main topics draw the student's attention to multi-disciplinary, chemistry-driven approaches to achieve a common goal - due to this, synthetic and analytical disciplines and techniques are often referred to in various contexts (for example, the use of NMR spectroscopy in the generation of molecular target models, and in the evaluation of target-ligand interactions).
Expected learning outcomes
After this course, the student will understand:
- the role of medicinal chemistry in drug discovery, including rational design and structural optimization of hits and leads (i.e., computational, chemical, biophysical sciences), and multiple examples related to their application to modern pharmaceutical research;
- how organic chemistry helps to identify new molecular targets through small molecule modulators of characterized (structure-based drug design, SBDD), or non- characterized molecular targets (ligand-based drug design, LBDD);
- the basics of NMR spectroscopy, including chemical shifts, integrals and coupling constants, the analysis of 1H and 13C 1D-NMR spectra and 2D-NMR techniques;
- applications of NMR to target-ligand interactions, including knowledge of various interaction techniques and their applications for the study of ligand-receptor interactions, and for the development of new biologically active molecules.
- the role of medicinal chemistry in drug discovery, including rational design and structural optimization of hits and leads (i.e., computational, chemical, biophysical sciences), and multiple examples related to their application to modern pharmaceutical research;
- how organic chemistry helps to identify new molecular targets through small molecule modulators of characterized (structure-based drug design, SBDD), or non- characterized molecular targets (ligand-based drug design, LBDD);
- the basics of NMR spectroscopy, including chemical shifts, integrals and coupling constants, the analysis of 1H and 13C 1D-NMR spectra and 2D-NMR techniques;
- applications of NMR to target-ligand interactions, including knowledge of various interaction techniques and their applications for the study of ligand-receptor interactions, and for the development of new biologically active molecules.
Lesson period: First semester
Assessment methods: Esame
Assessment result: voto verbalizzato in trentesimi
Single course
This course can be attended as a single course.
Course syllabus and organization
Single session
Responsible
Lesson period
First semester
Course syllabus
SENECI'S MODULE (3 CFUs)
- Chemical genetics in target ID and validation: elucidation of complex diseases mechanisms (cancer, neurodegeneration) using active compounds from phenotypic assays; identification and validation of druggable molecular targets and useful leads - bromodomains/inflammation, kinesin Eg5/cancer;
- Rational design and structural optimization of biologically active compounds: basic principles of molecular modeling; molecular descriptors for in silico models of biologically active organic molecules; chemical and biological similarity; chemical diversity collections in drug discovery - rational design and optimization of HSP90 inhibitors;
VASILE'S MODULE (3 CFUs)
- Basic principles of Nuclear Magnetic Resonance: NMR signals, chemical shifts, influence of neighboring atoms, effect of bond electrons; nuclei equivalence and NMR signal intensity (chemical and magnetic equivalence of nuclei, dynamic processes, definition of spin system); spin-spin coupling (NMR signal multiplicity); 13C NMR spectroscopy (13C chemical shift and intensity, DEPT experiments); multiple summary exercises;
- NMR determination of target-ligand interactions: Two-dimensional NMR spectroscopy (COSY, TOCSY, NOESY and HSQC spectra); NMR techniques to study the interactions between a small molecule (ligand, drug) and its receptor target (protein, DNA, RNA, membrane proteins); observation of macromolecule and ligand signals; multiple examples of applications of ligand-based techniques.
- Chemical genetics in target ID and validation: elucidation of complex diseases mechanisms (cancer, neurodegeneration) using active compounds from phenotypic assays; identification and validation of druggable molecular targets and useful leads - bromodomains/inflammation, kinesin Eg5/cancer;
- Rational design and structural optimization of biologically active compounds: basic principles of molecular modeling; molecular descriptors for in silico models of biologically active organic molecules; chemical and biological similarity; chemical diversity collections in drug discovery - rational design and optimization of HSP90 inhibitors;
VASILE'S MODULE (3 CFUs)
- Basic principles of Nuclear Magnetic Resonance: NMR signals, chemical shifts, influence of neighboring atoms, effect of bond electrons; nuclei equivalence and NMR signal intensity (chemical and magnetic equivalence of nuclei, dynamic processes, definition of spin system); spin-spin coupling (NMR signal multiplicity); 13C NMR spectroscopy (13C chemical shift and intensity, DEPT experiments); multiple summary exercises;
- NMR determination of target-ligand interactions: Two-dimensional NMR spectroscopy (COSY, TOCSY, NOESY and HSQC spectra); NMR techniques to study the interactions between a small molecule (ligand, drug) and its receptor target (protein, DNA, RNA, membrane proteins); observation of macromolecule and ligand signals; multiple examples of applications of ligand-based techniques.
Prerequisites for admission
Each student must know the fundamentals of chemistry and of organic chemistry (main organic compounds and reactions) in particular, through introductory chemistry courses of various BSc degrees. Basic notions of physics are also required.
Teaching methods
Interactive frontal lessons, where students are encouraged to attend and to actively participate; discussions are fostered, to improve their critical evaluation skills, to assimilate the presented concepts and ideas, and to verify proper understanding. Presented materials - pdf files, mp4 recordings if and when needed for Seneci's module - will be made available through the ARIEL website. For each topic, one or more examples will be described, to show the potential of chemistry-supported approaches in biology, and in particular in pharmaceutical research.
It is strongly recommended that students attend all the lectures.
It is strongly recommended that students attend all the lectures.
Teaching Resources
P. Seneci. Chemical Sciences in Early Drug Discovery. Elsevier, Amsterdam, 2018.
A. Randazzo. Guide to NMR spectral interpretation. A problem-based approach to determining the structures of small organic molecules. Loghia Publishing.
A. Randazzo. Guide to NMR spectral interpretation. A problem-based approach to determining the structures of small organic molecules. Loghia Publishing.
Assessment methods and Criteria
The learning assessment will involve a written exam at the end of the course, lasting two hours, and a compulsory Group Seminar (4-6 members per group) for the Seneci module. Students attending the course can opt for a mid-term examination plus a second partial exam at the end of the course, splitting the two main topics - organic synthesis-Seneci and analytical chemistry-Vasile.
The written exam includes open and multiple choice questions, chemical structures to be identified, charts and graphs to be completed; the earned mark will be the grade for Prof. Vasile's part, while for Prof. Seneci it will be the majority of the total mark. Group Seminars-Seneci will be delivered by teams of students, and will be evaluated looking at group (quality of ppt presentation, choice of presented papers) and individual parameters (individual presentations, answers to questions); the earned mark will contribute to a 1- to 3-point increment of the partial Seneci's mark.
The overall OCAB mark will be a 50/50 average of the marks earned with Prof. Vasile and Prof. Seneci.
The written exam includes open and multiple choice questions, chemical structures to be identified, charts and graphs to be completed; the earned mark will be the grade for Prof. Vasile's part, while for Prof. Seneci it will be the majority of the total mark. Group Seminars-Seneci will be delivered by teams of students, and will be evaluated looking at group (quality of ppt presentation, choice of presented papers) and individual parameters (individual presentations, answers to questions); the earned mark will contribute to a 1- to 3-point increment of the partial Seneci's mark.
The overall OCAB mark will be a 50/50 average of the marks earned with Prof. Vasile and Prof. Seneci.
CHIM/06 - ORGANIC CHEMISTRY - University credits: 6
Lessons: 48 hours
Professors:
Seneci Pierfausto, Vasile Francesca
Professor(s)