Automated solid-phase synthesis of cyclic peptides bearing a side-chain tail designed for subsequent chemical grafting. 1996

D Delforge, and M Art, and B Gillon, and M Dieu, and E Delaive, and M Raes, and J Remacle
Laboratory of Cellular Biochemistry, Facultés Universitaires N-D de la Paix (FUNDP), Namur, Belgium.

Recent developments in allyl chemistry and palladium solubilization allow automated continuous-flow solid-phase synthesis of cyclic or branched peptides, with specific side-chain cleavage and on-line cyclization. In this paper, we adapted the method to the synthesis of cyclic peptides bearing an anchoring tail on a side chain of the cycle. Side products were obtained with the standard procedure and an additional washing step had to be introduced in the synthesis protocol to remove side products resulting from the palladium allyl cleavage step. The method is illustrated by the automated synthesis of cyclo[-DVal-Arg-Gly-Asp-Glu (-epsilon Ahx-Cys-NH2)-] which contains the Arg-Gly-Asp adhesion motif (RGD) recognized by cellular integrins. The tail of the peptide was designed with a thiol at the carboxylic end to allow subsequent grafting by covalent attachment. Such tailed cyclic peptides can be grafted on different supports for new applications in biomaterial design, cell adhesion assays, affinity chromatography, immunization, vaccine development, ELISA kits, and the building of libraries of conformationally constrained peptides.

UI MeSH Term Description Entries
D010165 Palladium A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys.
D010456 Peptides, Cyclic Peptides whose amino acid residues are linked together forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS; some are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL). Circular Peptide,Cyclic Peptide,Cyclic Peptides,Cyclopeptide,Orbitide,Circular Peptides,Cyclopeptides,Orbitides,Peptide, Circular,Peptide, Cyclic,Peptides, Circular
D002623 Chemistry Techniques, Analytical Methodologies used for the isolation, identification, detection, and quantitation of chemical substances. Analytical Chemistry Techniques,Analytical Chemistry Methods,Analytical Chemistry Method,Analytical Chemistry Technique,Chemistry Method, Analytical,Chemistry Methods, Analytical,Chemistry Technique, Analytical,Method, Analytical Chemistry,Methods, Analytical Chemistry,Technique, Analytical Chemistry,Techniques, Analytical Chemistry
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001671 Biochemistry The study of the composition, chemical structures, and chemical reactions of living things.
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular

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