73870-83-4Relevant academic research and scientific papers
Development of supramolecular organo-gel based on tripeptide skeletons
Azuma, Eriko,Kuramochi, Kouji,Tsubaki, Kazunori
body text, p. 680 - 684 (2010/07/15)
Boc-Ser-Val-Gly-OCH2Ph (31) showed high gelation abilities in the aromatic solvents, particularly in toluene. The minimum gelation concentration of 31 in toluene was 10 mg/ml, suggesting that 2500 molecules of toluene were immobilized by each m
A novel resin linker for solid-phase peptide synthesis which can be cleaved using two sequential mild reactions
Zheng, Ailian,Shan, Daxian,Shi, Xuling,Wang, Binghe
, p. 7459 - 7466 (2007/10/03)
The interest in developing new linkers for solid-phase peptide and organic synthesis has increased tremendously as a result of the rapid development of combinatorial chemistry. Herein, we report the development of a new redox-sensitive linker for solid-phase peptide synthesis. This linker can be readily cleaved under mild conditions by using two sequential mild reactions, a reduction followed by a base (Bu4N+F-)-catalyzed cyclic ether formation. By using this new linker, two short peptides, a tetrapeptide [Boc- Trp-Ala-Gly-Gly-OH] and a pentapeptide [Boc-Asn-Ala-Ser(OBn)-Gly- Glu(OBn)OH)], were synthesized. Because the cleavage does not use acidic conditions, this resin linker provides an alternative when acidic conditions are not desirable. Furthermore, the cleavage conditions do not affect most of the side chain protecting group. Therefore, the peptides synthesized can be used for the segment synthesis of larger peptides without the need to reprotect the side chain functional groups.
Synthesis of a novel esterase-sensitive cyclic prodrug of a hexapeptide using an (acyloxy)alkoxy promoiety
Gangwar, Sanjeev,Pauletti, Giovanni M.,Siahaan, Teruna J.,Stella, Valentino J.,Borchardt, Ronald T.
, p. 1356 - 1362 (2007/10/03)
Synthetic methodology for preparing novel esterase-sensitive cyclic prodrugs of peptides with increased protease stability and cell membrane permeability compared to linear peptides is described. Cyclic prodrug 1 of the hexapeptide H-Trp-Ala-Gly-Gly-Asp-Ala-OH linked by the N-terminal amino group to the C-terminal carboxyl group via an (acyloxy)alkoxy promoiety was synthesized. A convergent synthetic approach involving Boc[[(alaninyloxy)methyl]carbonyl]-N-tryptophan (2) and H-Ala-Gly-Gly-Asp(OBzl)-OTce (3) was used. The key fragment 2 has the promoiety inserted between the Ala and the Trp residues. Fragment 3 was synthesized by a solution-phase approach using standard Boc-amino acid chemistry. These fragments were coupled to produce the protected linear hexapeptide, which after deprotection was cyclized using standard high-dilution techniques to yield cyclic prodrug 1. In pH 7.4 buffer (HBSS) at 37°C, cyclic prodrug 1 was shown to degrade quantitatively to the hexapeptide (t( 1/4 ) = 206 ± 11 min). The rate of hydrolysis of cyclic prodrug 1 was significantly faster in human blood (t( 1/4 ) = 132 ± 4 min) than in HBSS. Paraoxon, a known inhibitor of esterases, slowed this hydrolysis of cyclic prodrug 1 to a value (t( 1/4 ) = 198 ± 9 min) comparable to the chemical stability. In human blood, cyclic prodrug 1 was shown to be 25-fold more stable than the linear hexapeptide.
