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Free keywords:
ALLYLIC PROTECTING GROUPS; UNNATURAL AMINO-ACIDS; ACTIVATION IN-VIVO; N-RAS LIPOPEPTIDES; CHEMOENZYMATIC SYNTHESIS; H-RAS; PLASMA-MEMBRANE; TERMINAL LIPOHEXAPEPTIDE; INTERBILAYER TRANSFER; ENZYMATIC-SYNTHESIS
Biochemistry & Molecular Biology; Pharmacology & Pharmacy; bioorganic chemistry; biophysics; cell biology; protein lipidation; signal transduction;
Abstract:
Research in the biological sciences has undergone a fundamental and dramatic change during the last decades. Whereas biology was more phenomenologically oriented for a long time, today many biological processes are investigated and understood in molecular detail. It has become evident that all biological phenomena have a chemical basis: Biology is based on chemical principles. In the past, this insight had led to the development of biochemistry, molecular biology, and modern pharmacology. Today it increasingly determines the manner in which various biological phenomena are studied. The tools provided by classical biological techniques often are not sufficient to address the prevailing issues in precise molecular detail. Instead, the strengths of both chemical and biological methodology have to be used. Several recent research projects have proven that combining the power of organic synthesis with cell biology may open up entirely new and alternative opportunities for the study of biological problems. In this review we summarize the successful interplay between three disciplines-organic synthesis, biophysics, and cell biology-in the I study of protein lipidation and its relevance to targeting of proteins to the plasma membrane of cells in precise molecular detail. This, interplay is highlighted by using the Ras protein asa representative example. The development of methods for the synthesis of Ras-derived peptides and fully functional Ras proteins, the determination of their biophysical properties, in particular the ability to: bind to model membranes, and finally the use of synthetic Ras peptides and Pas proteins in cell biological experiments are. addressed. The successful combination of these three disciplines has led to a better understanding of the factors governing the selective targeting of Ras and related lipid-modified proteins to the plasma membrane.
