Medicinal Chemistry and Bioprocesses

During the lectures on Medicinal Chemistry the following topics will be illustrated:
1 Introduction to Medicinal Chemistry:
The discovery and development of new drugs. Biotechnology for the discovery and development of new drugs.
Molecular mechanisms of drug action and drug targets.
Receptors as targets for drugs.
Enzymes as targets for drugs.
Nucleic acids as targets for drugs.
2. Drug design and development:
Sources of research for lead compounds.
New "Drug design" strategies.
Structure-activity relationships (SAR). Pharmacophore research.
Optimization of drug interaction with the target. Chemical similarity.
Bioisosteric and stereochemical aspects of drug action.
Chemical-physical and biopharmaceutical properties of drugs and pharmacokinetics
Drug design aimed at optimizing drug access to the target.
Prodrugs.
Peptidomimetics.
Quantitative Relationships Structure-Activity (QSAR)
3. Notes on combinatorial chemistry.
During the discussion of the aforementioned topics, numerous references will be made to various types of drugs. In particular, the following classes of drugs will be explored:
· Antibiotics
· Anti-cancer drugs (selected examples).

With regard to the part of the course concerning the Fermentation Processes in the production of drugs, the following topics will be treated:
1. Fermentation process flow sheet: upstream and downstream
2. Microorganisms selection: screening, primary and secondary test, library construction and their characteristics
3. Characteristics of industrial strains and their conservation. Microorganisms of industrial interest for the production of secondary metabolites of pharmaceutical interest: actinomycetes and fungi. Yeasts and bacteria of industrial interest for the production of heterologous proteins: Pichia pastoris, Saccharomyces cerevisiae, Escherichia coli. Strain improvement.
4. Secondary metabolism in relation to the production of biologically active molecules. Characteristics, correlation with primary metabolism, regulation and catabolite repression. Gene clusters and general patterns of metabolic pathways
5. Upstream i) preparation of master and working cells banks, ii) inoculum,: vegetative, fermentative, chemically defined and complex culture medium, iii) raw carbon and nitrogen sources (molasses, corn steep liquor ...), growth factors, anti-foam. Development of industrial culture mediums. Case study.
6. Selection of the type of culture: solid, semi-solid, submerged, stationary. Fermenters: general characteristics, process variables, temperature control, agitation, aeration, sensors. Sterilization and pre-fermentation line.
7. Description of the fermentative processes through the Gaden curves, growth curves in relation to the production of primary and secondary metabolites. Batch, fed-batch and continuous processes. Productivity.
8. Dowmstream: general considerations about the choice of recovery techniques on industrial scale. Solid-liquid separation, primary isolation, high-resolution purification and formulation.