of natural or chemically modified nucleosides. The oligonucleotide chain assembly proceeds in the direction from 3'- to 5'-terminus by following a procedure referred to as a "synthetic cycle". Completion of a single synthetic cycle results in the addition of one nucleotide residue to the growing chain. The maximum length of synthetic oligonucleotides hardly exceeds 200 nucleotide components. From its current range of applications in basic research as well as in drug target validation, drug discovery, and therapeutic development, the potential use of oligonucleotides is foreseen in gene therapy (antisense drugs), disease prevention and agriculture. Antibody-drug conjugates (ADC) constitute a combination between small and big molecules. The small molecule parts, up to four different APIs, are highly potent cytotoxic drugs. They are linked with a monoclonal antibody, a big molecule which is of little or no therapeutic value in itself, but extremely discriminating for its targets, the cancer cells. The first commercialized ADCs were Isis's Fomivirsen and, more recently, Pfizer's (formerly Wyeth) Mylotarg (gemtuzumab ozogamicin). Examples of ADCs in phase III of development are Abbott's / Isis's Alicaforsen and Eli Lilly's Aprinocarsen. Technologies Several key technologies are used for the production of fine chemicals, including Chemical synthesis, either from petrochemical starting materials or from natural products extracts Biotechnology, for small molecules biocatalysis (enzymatic methods), biosynthesis (fermentation), and, for big molecules, cell culture technology Extraction from animals, microorganisms, or plants; isolation and purification, used, for example, for alkaloids, antibacterials (especially penicillins), and steroids Hydrolysis of proteins, especially when combined with ion exchange chromatography, used, for instance, for amino acids Chemical synthesis and biotechnology are most frequently used; sometimes also in combination. Traditional chemical synthesis A large toolbox of chemical reactions is available for each step of the synthesis of a fine chemical. The reactions have been developed on laboratory scale by academia over the last two centuries and subsequently adapted to industrial scale, for instance for the manufacture of dyestuffs & pigments. The most comprehensive handbooks describing organic synthetic methods is Methods of Molecular Transformations. About 10% of the 26,000 synthetic methods described therein are currently used on an industrial scale for fine chemicals production. Amination, condensation, esterification, Friedel–Crafts, Grignard, halogenation (esp. chlorination), and hydrogenation, respectively reduction (both catalytic and chemical) are most frequently mentioned on the websites of individual companies. Optically active cyanohydrins, cyclopolymerization, ionic liquids, nitrones, oligonucletides, peptide (both liquid- and solid-phase), electrochemical reactions (e.g., perfluorination) and steroid synthesis are