9-Fluorenylmethyloxycarbonyl/tbutyl-based convergent protein synthesis

Abstract

Besides linear solid phase peptide synthesis, segment condensation in solution and chemical ligation, convergent peptide synthesis (CPS) was developed in order to enable the efficient preparation of complex peptides and small proteins. According to this synthetic strategy, solid phase synthesized and suitably protected peptide fragments corresponding to the entire peptide/protein‐sequence are condensed on a solid support or in solution, to the target protein. This review summarizes CPS performed utilizing the mild 9‐fluorenylmethyloxycarbonyl/tbutyloxycarbonyl‐based protecting scheme for the amino acids. © 1999 John Wiley & Sons, Inc. Biopoly 51: 266–278, 1999

An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT1 Angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies

“…The preparation of the target compound V8 is depicted at Scheme 2. Firstly, selective tritylation [46][47][48][49][50] of N-1 nitrogen of compound 5 by trityl chloride (TrCl) in the presence of triethylamnie (TEA) led to 6. Subsequent alkylation of the N-3 nitrogen was carried out using the brominated biphenyl trityl tetrazole derivative 3 as alkylating agent, afforded 7 in good yield (65-70%).…”

“…compared to the Tr group [46][47][48][49][50]. Introduction of chlorine atom in the phenyl ring of Tr group produces more stable carbocation through hyperconjugation, compared to Tr carbocation.…”

Proteases as Powerful Catalysts for Organic Synthesis

“…Better recognition by antibodies can be obtained when using constrained structure peptidomimetics in which the amino acids comprising a region of a defined structure in the natural peptide are synthesized and bound by its N-and C-termini through a nonprotein ligand [180,181]. Peptides of less than 30 amino acid residues are mainly produced by sequential SPPS [163], while larger peptides (up to 60 residues) must be produced by convergent synthesis in which protected peptide fragments are synthesized by SPPS and then linked by liquid-phase synthesis [184]. Production of peptides on a large scale presents several challenges.…”

Synthesis Concepts for Peptides and Proteins

“…Placing Gly in this position excludes epimerization, which is also normally minimized in the case of Pro. Barlos and Gatos [63] studied the extent of epimerization of the C-terminal residue Glu 94 during condensation of the prothymosin a (ProTa) segments ProTa-(87-94) and ProTa-(95-109) using various coupling reagents and solvent systems. Methods to quantify the extent of epimerization that might occur in a given segment coupling have been described [87,88].…”