211746-09-7Relevant articles and documents
Synthesis and CD spectra of fluoro- and hydroxy-substituted β-peptides
Gessier, Francois,Noti, Christian,Rueping, Magnus,Seebach, Dieter
, p. 1862 - 1870 (2007/10/03)
β-Amino acids 1-3 with OH and F substituents in the α-position have been prepared (Scheme) from the natural (S)-α-amino acids alanine, valine, and leucine, and incorporated into β-hexa- and β-heptapeptides 4-12. The peptide syntheses were performed according to a conventional solution strategy (Boc/Bn protection) with fragment coupling. The new β-peptides with (series a) and without (series b) terminal protection were isolated in HPLC-pure form and characterized by NMR spectroscopy and MALDI mass spectrometry. The chemical properties as well as the patterns of the CD spectra (Figs. 3-5) depend upon constitution (OH, F, F2 substitution) and configuration (l or u) of the amino acid residues, upon the total number of OH and F substituents in the peptide chain, and upon the solvent used (H2O, MeOH, CF3CH2OH, (CF3)2CHOH). No reliable clues regarding the structures can be obtained from these CD spectra. Only a full NMR analysis will be able to answer the questions: a) with which known secondary structures (Figs. 1 and 2) of β-peptides are the OH and F derivatives compatible? b) Are new secondary structures enforced by the polar and/or H-bonding backbone substituents? Furthermore, the β-peptides described here will enable us to study changes in chemical, enzymatic, and metabolic stability, and in physiological properties caused by the heteroatoms.
Peptidomimetic inhibitors of the human cytomegalovirus protease
Ogilvie, William,Bailey, Murray,Poupart, Marc-André,Abraham, Abraham,Bhavsar, Amit,Bonneau, Pierre,Bordeleau, Josée,Bousquet, Yves,Chabot, Catherine,Duceppe, Jean-Simon,Fazal, Gulrez,Goulet, Sylvie,Grand-Ma?tre, Chantal,Guse, Ingrid,Halmos, Ted,Lavallée, Pierre,Leach, Michael,Malenfant, Eric,O'Meara, Jeff,Plante, Raymond,Plouffe, Céline,Poirier, Martin,Soucy, Fran?ois,Yoakim, Christiane,Déziel, Robert
, p. 4113 - 4135 (2007/10/03)
The development of peptidomimetic inhibitors of the human cytomegalovirus (HCMV) protease showing sub-micromolar potency in an enzymatic assay is described. Selective substitution of the amino acid residues of these inhibitors led to the identification of tripeptide inhibitors showing improvements in inhibitor potency of 27-fold relative to inhibitor 39 based upon the natural tetrapeptide sequence. Small side chains at P1 were well tolerated by this enzyme, a fact consistent with previous observations. The S2 binding pocket of HCMV protease was very permissive, tolerating lipophilic and basic residues. The substitutions tried at P3 indicated that a small increase in inhibitor potency could be realized by the substitution of a tert-leucine residue for valine. Substitutions of the N- terminal capping group did not significantly affect inhibitor potency. Pentafluoroethyl ketones, α,α-difluoro-β-keto amides, phosphonates and α- keto amides were all effective substitutions for the activated carbonyl component and gave inhibitors which were selective for HCMV protease. A slight increase in potency was observed by lengthening the P1' residue of the α-keto amide series of inhibitors. This position also tolerated a variety of groups making this a potential site for future modifications which could modulate the physicochemical properties of these molecules.
An enantioselective, stereodivergent approach to anti- and syn-α-hydroxy-β-amino acids from anti-3-amino-1,2-diols. Synthesis of the ready for coupling Taxotere side chain
Pasto, Mireia,Moyano, Albert,Pericas, Miquel A.,Riera, Antoni
, p. 243 - 262 (2007/10/03)
Both anti- and syn-α-hydroxy-β-amino acids are efficiently synthesised in protected form and high enantiomeric purity from readily available anti-N-Boc-1-tert-butyldimethylsilyl-3-amino-1,2-diols. The preparation of the anti series is straightforward, and
