150447-60-2Relevant academic research and scientific papers
Access to Enantiopure α-Hydrazino Acids for N-Amino Peptide Synthesis
Kang, Chang Won,Sarnowski, Matthew P.,Elbatrawi, Yassin M.,Del Valle, Juan R.
, p. 1833 - 1841 (2017/02/10)
Backbone N-methylation of α-peptides has been widely employed to enhance the bioavailability and bioactivity of parent sequences. Heteroatomic peptide amide substituents have received less attention due, in part, to the lack of practical synthetic strategies. Here, we report the synthesis of α-hydrazino acids derived from 19 out of the 20 canonical proteinogenic amino acids and demonstrate their use in the solid-phase synthesis of N-amino peptide derivatives.
Solid-phase synthesis of tetrahydropyridazinedione-constrained peptides
Kang, Chang Won,Ranatunga, Sujeewa,Sarnowski, Matthew P.,Del Valle, Juan R.
supporting information, p. 5434 - 5437 (2015/02/19)
The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported. The described protocol features the synthesis of chiral α-hydrazino acids suitable for chemoselective incorporation into growing peptide chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage affords the target peptidomimetics in good yield and purity. The scope of Tpd incorporation is demonstrated through the synthesis of constrained peptides featuring nucleophilic/electrophilic side chains and sterically encumbered α-substituted hydrazino acid residues. (Chemical Equation Presented).
Ribosome-mediated incorporation of hydrazinophenylalanine into modified peptide and protein analogues
Killian, Jennifer A.,Van Cleve, Mark D.,Shayo, Yuda F.,Hecht, Sidney M.
, p. 3032 - 3042 (2007/10/03)
(S)-α-Hydrazinophenylalanyl-tRNA(Phe), an aminoacyl-tRNA derivative containing the unnatural amino acid (S)-α-hydrazinophenylalanine, was prepared in an effort to examine the stereochemical requirements of the A- site of the ribosome during in vitro protein synthesis. The (S)-α- hydrazinophenylalanine moiety was of interest because it contains two nucleophilic centers, the secondary nitrogen attached to C(α), which is normally acylated during the course of peptide bond formation, and the sterically less hindered primary nitrogen. To determine the position of acylation, (S)-α-hydrazinophenylalanyl-tRNA(Phe) was tested in an Escherichia cull in vitro protein biosynthesizing system lacking elongation factor G, such that only dipeptide products were formed. The dipeptide product mixture was analyzed by HPLC in direct comparison with authentic synthetic standards. The dipeptide assay utilizing (S)-α- hydrazinophenylalanyl-tRNA(Phe) as the A-site tRNA established that the analogue functioned well as an acceptor tRNA; HPLC analysis of the products showed that both dipeptides were formed in approximately equal amounts. When attached to a suppressor tRNA transcript, (S)-α-hydrazinophenylalanine was also incorporated into position 27 of dihydrofolate reductase in an E. coli protein synthesizing system by readthrough of a nonsense codon. This finding expands the currently accepted model of peptide bond formation at the ribosome and adds to the repertoire of peptide-like products shown to form at the peptidyltransferase center of the ribosome.
Conformationally constrained nonpeptide β-turn mimetics of enkephalin
Gardner, Benjamin,Nakanishi, Hiroshi,Kahn, Michael
, p. 3433 - 3448 (2007/10/02)
The design, synthesis and in vitro biological analysis of a family of conformationally constrained nonpeptide mimetics incorporating a 4→1 β-turn prosthetic unit to examine the proposed biological significance of this conformer is described.
THE PREPARATION OF 2-HYDRAZINYL ESTERS IN HIGH OPTICAL PURITY FROM 2-SULFONYLOXY ESTERS
Hoffmann, Robert V.,Kim, Hwa-Ok
, p. 2953 - 2956 (2007/10/02)
Chiral 2-triflyloxy esters, prepared from chiral 2-hydroxy esters, react enantiospecifically with BocNHNH2 to produce optically pure 2-hydrazinyl ester derivatives in high yields.The reaction of 2-nosyloxy esters with BocNHNH2 gives 2-(Boc-hydrazinyl) esters, thus providing an efficient (albeit slow) method for the conversion of esters to 2-hydrazinyl ester derivatives.
