Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:2270-20-4 (5-phenylpentanoic acid)
 26 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four cyclic dehydrodipeptides, cyclo (-delta aminoacyl-L-Ala-), in which aminoacyl is Phe, Apb (2-amino-4-phenylbutanoic acid), App (2-amino-5-phenylpentanoic acid) and Aph (2-amino-6-phenylhexanoic acid), were prepared by condensation of cyclo (-N-Ac-Gly-N-Ac-L-Ala-) with the corresponding aldehydes. Among them, the yield of cyclo (-delta Apb-L-Ala-) was exceptionally low. Each compound was hydrogenated in the presence of Pd black at various temperatures and chiral induction in hydrogenation was evaluated. Low chiral induction at high temperature (50 degrees) was observed in the case of cyclo (-delta Phe-L-Ala-). Optically pure L-Apb, L-App and L-Aph were obtained from the corresponding cyclic dehydrodipeptides, respectively, by hydrogenation and subsequent acid hydrolysis.
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PMID:Cyclic peptides. XIII. Asymmetric synthesis of aromatic L-alpha-amino acids through hydrogenation of cyclic dehydrodipeptides. 682 78

A number of cyclo (delta aminoacyl-L-aminoacyl) (delta aminoacyl = delta Aba, delta Val, delta Leu, delta App, delta Phe and delta Trp; L-aminoacyl=L-Ala, L-Val, L-Leu and L-Lys (epsilon-Ac)) were synthesized by the condensation of cyclo (N-acetyl-Gly-N-acetyl-L-aminoacyl) with corresponding aldehyde or acetone and subsequent treatment with hydrazine. Each cyclo (delta aminoacyl-L-aminoacyl) except ones containing delta Phe and delta Trp was hydrogenated using Pd black in methanol to give cyclo (L-aminoacyl-L-aminoacyl) with high chiral induction. In the case of dehydro-cyclodipeptides containing delta Phe or delta Trp, slightly lower chiral induction was observed. Then, a mechanism of asymmetric hydrogenation was proposed. The influence of variation of solvent, temperature and catalyst on asymmetric hydrogenation was examined. Optically pure L-2-aminobutanoic acid, L-2-amino-5-phenylpentanoic acid and L-phenylalanine were synthesized on a preparative scale by this method and subsequent acid-hydrolysis.
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PMID:Cyclic peptides. IX. Asymmetric hydrogenation of alpha, beta-dehydroamino acid residue in cyclodipeptides and preparation of optically pure alpha-amino acids. 746 7

Plasmodium falciparum is a major causative agent of malaria, a disease of worldwide importance. Inhibition of a hemoglobin degrading P. falciparum aspartic protease Plasmepsin II (Plm II) provides a viable strategy for antimalarial therapy. Linear peptidic inhibitors based on the 4(S)-amino-3(S)-hydroxy-5-phenylpentanoic acid at the P1-P1' positions are known which inhibit Plm II with improved selectivity over cathepsin D. A series of computations were performed in order to gain insight into the interactions of these inhibitors with Plm II. The docking and molecular dynamics simulations were performed on a model ligand/enzyme complex to optimize the variables involved in the generation of ligand/enzyme models. This protocol of docking and molecular dynamics (MD) simulation was then used to derive the ligand-enzyme complexes of the molecules used in the present study. Different modes of binding of pepstatin and the three linear inhibitors were studied. Molecular dynamics simulation was performed at 300K for 100ps with a time step of Ifs. The structural effects of ligand binding were analyzed on the basis of hydrogen bond interactions, interaction energies, hydrophobic contacts and RMS deviations in the resulting energy-minimized structures of the receptor-ligand complexes. The results indicate that hydrophobic and hydrogen bonding interactions are responsible for selective inhibition of Plm II and improved selectivity over cathepsin D. Hydrogen bonding interaction plays an important role for amino acid residues such as Asp-34, Asp-214, Thr-217, Ser-218, Val-78, Ser-79, Tyr-192 and Gly-216. The binding of the inhibitors to the enzyme, while producing no large distortions in the enzyme active site cleft, results in significant RMS deviations of the inhibitor, which represent the distortion of the inhibitor, effected by the proteinase. Thus, the information generated from this analysis should be useful for further work in the area of antimalarial research.
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PMID:Molecular dynamics simulations of the three dimensional model of plasmepsin II-peptidic inhibitor complexes. 1176 33