Peptides template-mediated

Template-mediated ligation, an approach to bring two peptide fragments into close proximity. The N-terminus of one peptide and C-terminus of the other peptide are attached to a template, and consequently close to each other so that they can form a peptide bond. The basic principle was created by Brenner et al. using a salicylamide template based on a base-catalyzed intramolecular rearrangement and has been later exploited in thiol capture ligation [M. Bretmer et al., Helv. Chim. Acta 1957, 40, 1497]. 

Thiol capture ligation, a variant of template-mediated ligation used for amide bond formation between two unprotected peptide fragments. According to Kemp, a 4-hydroxy-6-mercaptodibenzofuran template with a hydroxy and a thiol substituent has been employed. One peptide is connected with its C-terminus to the hydroxyl substituent, while the other peptide containing an N-terminal Cys residue is connected to the template thiol across a disulfide bond. This brings the N-terminus of one peptide and C-terminus of the other peptide into close proximity, and the amide bondforming step occurs as a very rapid in-... 

Cellular protein biosynthesis involves the following steps. One strand of double-stranded DNA serves as a template strand for the synthesis of a complementary single-stranded messenger ribonucleic acid (mRNA) in a process called transcription. This mRNA in turn serves as a template to direct the synthesis of the protein in a process called translation. The codons of the mRNA are read sequentially by transfer RNA (tRNA) molecules, which bind specifically to the mRNA via triplets of nucleotides that are complementary to the particular codon, called an anticodon. Protein synthesis occurs on a ribosome, a complex consisting of more than 50 different proteins and several stmctural RNA molecules, which moves along the mRNA and mediates the binding of the tRNA molecules and the formation of the nascent peptide chain. The tRNA molecule carries an activated form of the specific amino acid to the ribosome where it is added to the end of the growing peptide chain. There is at least one tRNA for each amino acid. 

In addition to incorporating the 4-(2-aminoethyl)dibenzofuran-6-propanoic acid template into small peptides where a reverse turn is desired, we have also recently incorporated this template into a mini-protein called the PIN WW domain. WW domains have a three-stranded antiparallel p-sheet structure that mediates intracellular protein-protein interactions. 31 Substitution of this 3-turn mimetic into loop 1 of the PIN WW domain leads to a folded, three-stranded, antiparallel p-sheet structure with a stability indistinguishable from that of the all a-amino acid sequence. The template-incorporated PIN WW domain (11) was synthesized by an Fmoc-based solid-phase peptide synthesis strategy (Scheme 8), utilizing N-Fmoc-protected 4-(2-aminoethyl)dibenzofuran-6-propanoic acid 10. 11 The synthesis of 10, similar to that of 8, has been published.1 1 ... 

Biomimetic processes other than inorganic crystallisation have also been described. Wright and co-workers templated the production of the polymer hemozoin, a crystalline heme aggregate used by malarial parasites in a detoxification process. Understanding and controlling this could lead to new antimalarial drugs. Peptide dendrimers containing multiple repeats of the Ala-His-His sequence known to mediate hemozoin formation were prepared and indeed were shown to induce its production. ... 

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