The rate of multidrug-resistant infections is rapidly rising. Cationic antibacterial peptides are both active against resistant pathogens and have low propensity for resistance development, but due to their unfavourable medicinal properties cationic antib acterial peptides have yet been a limited clinical success. We have found that introduction of non-genetically coded amino acids and other lipophilic modifications opens the opportunity for development of extremely short and highly active antibacterial pe ptides with improved medicinal properties. The present project is aimed towards finding novel methods of avoiding proteolytic degradation of antibacterial peptides by an integrated medicinal chemistry approach. A majority of the work outlined in the proje ct is priented into adaption or development of new synthetic methods for solid phase diversity library preparation. Strong interaction with computational biologists and medicinal chemists is however emphasised.