Pilkington-Miksa, M.; (2005) The synthesis of modified integrin-targeting peptides for incorporation into lipid/integrin-targeting peptide/DNA transfection complexes. Doctoral thesis , University of London.

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Abstract

Integrin-targeting peptides have been shown to increase transfection efficiency when included in a number of different non-viral vectors. In the case of Lipofectin/DN A complexes (LD), transfection efficiency has been shown to increase on incorporation of an integrin- targeting peptide (Lipid/Integrin-targeting peptide/DNA complexes), as seen by a 100-fold increase in luciferase expression. Efforts to improve the Lipofectin component of Lipid/Integrin-targeting peptide/DNA complexes continue to be made and consequently ways of increasing transfection efficiency through modifications to the integrin-binding peptide are also been investigated. The integrin- targeting peptide component of Lipid/Integrin-targeting peptide/DNA complexes investigated by Hart et al. has effectively three functionalities a 'head' which is complimentary to a specific integrin, a 'tail' which can bind to and condense DNA and a 'spacer' which links the 'head' and 'tail'. Both alternative spacers and DNA-binding motifs have been synthesised and incorporated into integrin-targeting peptides with the intention of investigating the effects of these modifications on the transfection efficiency as well as physical properties of Lipid/Integrin-targeting peptide/DNA complexes. In this thesis are reported the structures of unnatural amino acids synthesised and incorporated into integrin-targeting peptides, as well as some of the transfection results obtained.

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