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Peptides as drugs: myth or reality? Peptides find many applications in the fields of biotechnology, among which pharmaceutical applications. Progression of the number of traditional drugs deposited at the FDA is slowing down. It’s the reason why many big pharmaceutical companies invest more and more in peptides to open new therapeutic perspectives. Even if some peptides have been used as therapeutic agents in their natural bioactive form for nearly one century, a significant development of the number of peptides has occurred since a few tenths of years, in particular due to the development of methods of production, chemical as solid phase as well as biological as phage display. Peptides have a number of advantages when compared to traditional drugs like small molecules, however their development encounters some limitations, which are relative to a low ability to cross membrane barriers and a low half-life time and a difficulty to understand their mechanism of action. A series of solutions can be brought to overcome these problems. Molecular modelling has an important role to play in this context, notably for the in silico determination of the structure, the stability and the polymorphism of peptides or for the study and the improvement of the capacity to bind a target

The implication of fusion peptides of class I viral fusion glycoproteins in the membrane fusion. Viral infection involves fusion between the viral envelope and the target cell plasmic membrane. The fusion is induced by a glycoprotein anchored in the viral envelope. After activation, the glycoprotein undergoes a conformational change inducing the exposure of a region named « fusion peptide » essential for the fusion process. Studies on glycoproteins and on isolated fusion peptides have allowed to better understand the mechanisms involved in membrane fusion. It was notably shown that fusion peptides induce fusion and leakage of membranes. These peptides are able to insert obliquely in a membrane when helical. This orientation induces lipid destabilisation, favouring membrane fusion. However, to date, none of these in vitro, in vivo or in silico studies has determined the minimal sequence required for membrane fusion. Using the obliquity-fusogenicity relationship, the latter was determined by molecular modelling for two viruses, the Human Immunodeficiency Virus and the Bovine Leukaemia Virus. These new results are of particular interest in the development of vaccines and antiviral drugs.

Liposomes: description, preparation and applications. Liposomes are spherical vesicles with a diameter ranging from 20 nm to a few thousands nm. These vesicles consist of one or several bilayers which separate an intravesicular from an external medium. Within these bilayers, like in the biological membrane, motion of phospholipids is observed. Liposomes are easy to prepare. The hydration of a phospholipidic film leads to the formation of multilamellar liposomes. Additional steps are required to form unilamellar liposomes. Liposomes are used for industrial purposes, such as the targeting of cosmetological compounds. They may also be used as therapy vectors, for drug delivery or as vaccine supports. Liposomes are good models for membranes and are widely used for improving the understanding of biological events that occur in cell membranes, such as permeability, fluidity, protein anchoring and fusion of membranes. This paper mainly emphasizes membrane fusion.

Outline of conformational analysis techniques of the biological macromolecules. This paper presents a synthesis of thevarious methods of conformational analysis of biological macromolecules usually quoted in the literature. The generalprinciples as well as the limitations and advantages of various experimental techniques are exposed. These techniques shouldnot be regarded as competitors but as complementary. To finish, a chapter is devoted to the presentation of a theoretical tool,the molecular modeling.