149357-59-5Relevant academic research and scientific papers
Efficient access to enantiopure γ4-amino acids with proteinogenic side-chains and structural investigation of γ4- asn and γ4-ser in hybrid peptide helices
Jadhav, Sandip V.,Misra, Rajkumar,Singh, Sumeet K.,Gopi, Hosahudya N.
supporting information, p. 16256 - 16262 (2013/12/04)
Hybrid peptides composed of α- and β-amino acids have recently emerged as new class of peptide foldamers. Comparatively, γ- and hybrid γ-peptides composed of γ4-amino acids are less studied than their β-counterparts. However, recent investigations reveal that γ4-amino acids have a higher propensity to fold into ordered helical structures. As amino acid side-chain functional groups play a crucial role in the biological context, the objective of this study was to investigate efficient synthesis of γ4-residues with functional proteinogenic side-chains and their structural analysis in hybrid-peptide sequences. Here, the efficient and enantiopure synthesis of various N- and C-terminal free-γ4-residues, starting from the benzyl esters (COOBzl) of N-Cbz-protected (E)-α,β-unsaturated γ-amino acids through multiple hydrogenolysis and double-bond reduction in a single-pot catalytic hydrogenation is reported. The crystal conformations of eight unprotected γ4-amino acids (γ4-Val, γ4-Leu, γ4-Ile, γ4-Thr(OtBu), γ4-Tyr, γ4-Asp(OtBu), γ4- Glu(OtBu), and γ-Aib) reveals that these amino acids adopted a helix favoring gauche conformations along the central Cγi￡ Cβ bond. To study the behavior of γ4- residues with functional side chains in peptide sequences, two short hybrid γ-peptides P1 (Ac-Aib-γ4-Asn-Aib-γ4-Leu- Aib-γ4-Leu-CONH2) and P2 (Ac-Aib- γ4-Ser-Aib-γ4-Val-Aib-γ4-Val- CONH2) were designed, synthesized on solid phase, and their 12-helical conformation in single crystals were studied. Remarkably, the γ4-Asn residue in P1 facilitates the tetrameric helical aggregations through interhelical H bonding between the side-chain amide groups. Furthermore, the hydroxyl side-chain of γ4-Ser in P2 is involved in the interhelical H bonding with the backbone amide group. In addition, the analysis of 87 γ4-residues in peptide single-crystals reveal that the γ4-residues in 12-helices are more ordered as compared with the 10/12- and 12/14-helices. Copyright
Dihydroxyacetone phosphate aldolase catalyzed synthesis of structurally diverse polyhydroxylated pyrrolidine derivatives and evaluation of their glycosidase inhibitory properties
Calveras, Jordi,Egido-Gabas, Meritxell,Gomez, Livia,Casas, Josefina,Parella, Teodor,Joglar, Jesus,Bujons, Jordi,Clapes, Pere
scheme or table, p. 7310 - 7328 (2010/03/24)
The chemoenzymatic synthesis of a collection of pyrrolidine-type iminosugars generated by the aldol addition of dihydroxyacetone phosphate (DHAP) to C-α-substituted N-Cbz-2-aminoaldehydes derivatives, catalyzed by DHAP aldolases is reported. L-Fuculose-1-phosphate aldolase (FucA) and L-rhamnulose-1-phosphate aldolase (RhuA) from E. coli were used as biocatalysts to generate configurational diversity on the iminosugars. Alkyl linear substitutions at C-α were well tolerated by FucA catalyst (i.e., 40-70% conversions to aldol adduct), whereas no product was observed with C-α-alkyl branched substitutions, except for dimethyl and benzyl substitutions (20%). RhuA was the most versatile biocatalyst: C-α-alkyl linear groups gave the highest conversions to aldol adducts (60-99%), while the C-α-alkyl branched ones gave moderate to good conversions (50-80%), with the exception of dimethyl and benzyl substituents (20%). FucA was the most stereoselective biocatalyst (90-100% anti (3R,4R) adduct). RhuA was highly stereoselective with (S)-N-Cbz-2-aminoaldehydes (90-100% syn (i.e., 3R,4S) adduct), whereas those with R configuration gave mixtures of antilsyn adducts. For iPr and iBu substituents, RhuA furnished the anti adduct (i.e., FucA stereochemistry) with high stereoselectivity. Molecular models of aldol products with iPr and iBu sub-stituents and as complexes with the RhuA active site suggest that the and adducts could be kinetically preferred, while the syn adducts would be the equilibrium products. The polyhydroxylated pyrrolidines generated were tested as inhibitors against seven glycosidases. Among them, good inhibitors of a-L-fucosidase (IC50 = 1-20 μM), moderate of α-L-rhamnosidase (IC50=7-150 μM), and weak of α-D-mannosidase (IC50 = 80-400 μM) were identified. The apparent inhibition constant values (Ki) were calculated for the most relevant inhibitors and computational docking studies were performed to understand both their binding capacity and the mode of interaction with the glycosidases.
Aza-Wittig rearrangement of N,N-dipropargylic α-amino alkyllithiums: Periselectivity and steric course
Tomoyasu, Takahiro,Tomooka, Katsuhiko
, p. 1925 - 1928 (2007/10/03)
The aza-Wittig rearrangement of enantio-defined N,N-dipropargylic α-amino alkyllithiums, generated by tin-lithium exchange, are shown to afford [1,2]- and/or [2,3]-rearrangement products. Both aza-Wittig rearrangements proceed predominantly with inversion of configuration at the Li-bearing carbon terminus.
Aminoalkyl-substituted α-methylene-γ-butyrolactones from α-amino acids using an indium-mediated Barbier allyl addition
Steurer, Steffen,Podlech, Joachim
, p. 1551 - 1560 (2007/10/03)
The indium-mediated reaction of Z-protected α-amino aldehydes 1-6 with 2-(bromomethyl)acrylates 8/9 in aqueous solvents has been investigated. The preference for the formation of syn-configured homoallyl alcohols 10-16 (diastereoselectivities ranging from
A second-generation cycloaddition route to 5-substituted 3-acyltetramic acids
Jones, Raymond C. F.,Dawson, Claire E.,O'Mahony, Mary J.
, p. 873 - 876 (2007/10/03)
The 1,3-dipolar cycloaddition of α-aminonitrile oxides, formed from α- amino-acids, to enamines of β-ketoesters affords 3-(1-aminoalkyl)isoxazole- 4-carboxylic esters that are convened via pyrrolo[3,4-c]isoxazol-4-ones into 5-substituted 3-acetyltetramic
Design of a potent combined pseudopeptide endothelin-a/endothelin-b receptor antagonist, ac-dBhg16-Leu-Asp-IIe-[NMe]IIe-Trp21 (PD 156252): Examination of its pharmacokinetic and spectral properties
Cody, Wayne L.,He, John X.,Reily, Michael D.,Haleen, Stephen J.,Walker, Donnelle M.,Reyner, Eric L.,Stewart, Barbra H.,Doherty, Annette M.
, p. 2228 - 2240 (2007/10/03)
The endothelins (ETs) are a family of bicyclic 21-amino acid peptides that are potent and prolonged vasoconstrictors. It has been shown that highly potent combined ET(A)/ET(B) receptor antagonists can be developed from the C- terminal hexapeptide of ET (H
