Synthesis and membrane association of hydrophobic peptides with covalently linked fatty acids

Abstract

Proteins undergo various modifications during or after translation. Several proteins of newlineprokaryotic, eukaryotic viral origins have been found to be modified with covalently linked newlinefatty acids and very recently modification with isoprene units have also been observed. newlineThere is extensive documentation about the proteins that are acylated, the sequences in the newlineregion o.f acylation and the enzymes that are involved in this modification. Most of the newlineproteins that are acylated perform important functions like regulating cell growth and these newlinemodification are required for their optimal functioning. However, there has not been much newlineinformation as to how covalently linked fatty acid might modulate the association of the newlinepeptide chain with membranes. Hence, work directed towards this was initiated. Synthetic newlinepeptides corresponding to the acylation regions in proteins and their fatty acyl derivatives newlinewere synthesized. Their conformations and interactions with membranes were investigated. newlineThe contents of this thesis are divided into six chapters and are as follows:- newlineChapter 1 : A brief description about the diverse group of structurally and functionally newlinedistinct proteins that are acylated, the various aspects of fatty acid acylation, the enzymes newlinethat are involved in these modifications and how these modifications are necessary for newlineoptimal functioning of these proteins are reviewed. newlineChapter 2 : The source of chemicals, purification of solvents, preparation of amino acid and newlinefatty acid derivatives, experimental protocols followed in solution and solid phase peptide newlinesynthesis, details of amino acid and fatty acid analysis and purification of lipids are newlinedescribed in this chapter. newlineIf newlineChapter 3 : This chapter deals with various protocols involved in the synthesis of peptides newlineand their fatty acyl derivatives. The general procedures followed and the details of newlineindividual peptides obtained by solution phase and segment condensation methods are newlinedescribed.