Organic chemistry applied to biology

A.A. 2021/2022
Crediti massimi
Ore totali
Obiettivi formativi
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).
Risultati apprendimento attesi
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.
Programma e organizzazione didattica

Edizione unica

Primo semestre
CONTENTS, MATERIAL - The program for the course will not be modified due to COVID-19, and the same is true for the reference material (slide copies on Ariel2, reference texts).
MODALITY - The virtual course room will be on the Microsoft Teams platform, and both instructors will be teaching in a syncronous manner; an mp4 copy of each lesson will then be stored on the Ariel2 Website, for the students to be easily accessed.
EXAMS - Written exams will take place using the Zoom platform, and detailed instructions will be provided - together with a mock Exam session - to the students at the end of the teaching sessions. Multiple choice questions will be used to test the students' knowledge in a 2 hours' exam. Intermediate exams (1 hour each) will be held for single modules (Vasile, Seneci) at the end of each module. If and when the COVID-19 emergency will allow it, written exam in UniMI rooms will also be organized.
SEMINARS - Group experiences (selection of a relevant paper, preparation of a ppt presentation, delivery to the class) will be used as an optional, additional exam format in Seneci's module.
- 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;
- 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.
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.
Metodi didattici
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 - 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 lectures.
Materiale di riferimento
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.
Modalità di verifica dell’apprendimento e criteri di valutazione
The learning assessment will involve a written exam at the end of the course, and an optional Group Seminar 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 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. Optional group Seminars-Seneci will be delivered by teams of students, and will be evaluated looking at common (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 total Seneci's mark.
Lezioni: 48 ore
venerdì 11.30-13.30