Biopolymers solid phase synthesis

Biologic Background Technical Background Synthesis of Biopolymers Solid-Phase Synthesis of Small Molecules... 

Resins and handles for solid-phase synthesis. In Kates SA, ed. Biopolymers Peptide Science. 1998 47 309-411. 

E. A. B. Kantchev, C.-C. Chang, and D.-K. Chang, Direct Fmoc/tert-Bu solid phase synthesis of octamannosyl polylysine dendrimer-peptide conjugates, Biopolymers, 84 (2006) 232-240. 

J Alsina, F Albericio. Solid-phase synthesis of C-terminal modified peptides. Biopolymers (Pept Sci) 71, 454, 2003. 

Burgess, K. Linthicum, D. S. Shin, H. Solid-Phase Synthesis of Unnatural Biopolymers Containing Repeating Urea Units, Angew. Chem. Int. Ed. Engl. 1995, 34, 907. 

For many years, most efforts directed towards the development of solid-phase preparations of alcohols had been limited to the synthesis of biopolymers, such as oligonucleotides and oligosaccharides. Interest in the preparation and chemical transformation of all types of alcohol on insoluble supports only began to grow rapidly in the early 1990s, when chemists realized the potential of parallel solid-phase synthesis for high-throughput compound production. 

Automated synthesis of peptide and oligonucleotide libraries was initiated about 10 years ago [4], Within the last three years, there has been much attention focused on the generation of combinatorial libraries of small molecules. As with biopolymers, the use of solid resin support was central to the advance of this field. In solid-phase synthesis, one of the reactants is covalently bound to the solid support and an excess of the other reactants may be used in each step to drive reactions to completion. Purification of the intermediates and final product is easily achieved through extensive washing of the resin after each chemical step. For the purpose of high throughput synthesis, cleavage of the final... 

Rasoul, F., Ercole, F., Pham, Y., et al. (2000) Grafted supports in solid-phase synthesis. Biopolymers (Pept. Sci.) 55, 207-216. 

The solid-phase synthesis of biopolymers via iterative coupling of monomeric building blocks has found widespread application. It can be adapted easily for the incorporation of non-natural building blocks or labeled monomers, which will be used as probe molecules in chemical biology. 

The inevitable comparison of polysac-chrides to other biopolymer types helps put the challenge into perspective. Nucleic acids are made in a linear manner through chemical and biological synthetic techniques. Likewise, protein sequences are also linear and can be easily determined, produced, and manipulated through a combination of recombinant DNA technology and solid phase synthesis. 

Solid-phase synthesis was first applied to the assembly of peptides [23-27] and subsequently extended to other biopolymers such as oligonucleotides [28-30] and oligosaccharides [31-34]. Solid-phase synthesis is particularly valuable for the construction of linear oligomers because their... 

Synthesis on solid supports was first developed by Merrifield [1] for the assembly of peptides. It has expanded to include many different applications including oligonucleotide, carbohydrate, and small-molecule assembly (see Chapters 11 and 14). The repetitive cycle of steps involved in the solid-phase synthesis of biopolymers can be performed manually using simple laboratory equipment or fully automated with sophisticated instrumentation. This chapter examines typical solid-phase reaction kinetics to identify factors that can improve the efficiency of both manual and automated synthesis. The hardware and software features of automated solid-phase instruments are also discussed. The focus of this discussion is not on particular commercial model synthesizers but on the basic principles of instrument operation. These considerations can assist in the design, purchase, or use of automated equipment for solid-phase synthesis. Most contrasting features have advantages and disadvantages and the proper choice of instrumentation depends on the synthetic needs of the user. 

Manual solid-phase synthesis requires intervention by a chemist during the assembly of a biopolymer. A manual synthesis can vary from manual addition of all reagents and solvents to manual intervention at a single step (such as addition of the monomer). 

In solid phase synthesis (SPS) of biopolymers, the peptide/nucleotide/glycoside chain is assembled in the nsnal manner (conventional approach) from the C-/3 -/NR-end. The first monomer unit of the biopolymer to be synthesized is connected via its car-boxyl/hydroxyl/hydroxyl gronp to an insoluble polymer. A necessary prerequisite is that anchoring groups (linkers) are introdnced into the polymeric material (step 1). The first protected monomer is then reacted with the functional gronp of the linker (step 2). The... 

Albericio F (2000) Orthogonal protecting groups for N -amino and C-terminal caiboxyl functions in solid-phase synthesis. Biopolymers (Peptide Sci) 55 123-139... 

TFMS CF3SO3H, M, 150.7, b.p. 162 C. TFMS is one of the strongest acids known, and has proved effective for the simultaneous deprotection and resin cleavage at the conclusion of the solid-phase synthesis of peptides, e.g. tuftsin, enkephalin, bovine pancreatic RNase and chicken neurotensin. [H.Yajima etal. Chem. Pharm. Bull. 29 (1981) 2587 H.Yajima N.Fujii Biopolymers 20 (1981) 1958 Y.Kiso etal. Chem. Pharm. Bull. 27 (1979) 1472 M.K.Chaudhuri V. A. Najjar i4na/. Biochem. 95 (1979) 305]... 

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