Access to α,α-Disubstituted Disilylated Amino Acids and Their Use in Solid-Phase Peptide Synthesis.

A concise synthetic pathway yielding to hydrophobic α,α-disubstituted disilylated amino acids based on a hydrosilylation reaction is described. As a first example of utilization in solid-phase peptide synthesis, TESDpg was introduced in replacement of Aib in an alamethicin sequence, leading to analogues with modified physicochemical properties and conserved helical structures. This study highlights the potential of these new amino acids as tools for peptide modulation.

[1]  Takashi Misawa,et al.  Synthesis of a bis-cationic α,α-disubstituted amino acid (9-amino-bispidine-9-carboxylic acid) and its effects on the conformational properties of peptides , 2015 .

[2]  Jean Martínez,et al.  Stereoselective synthesis of unsaturated α-amino acids , 2015, Amino Acids.

[3]  B. Vergani,et al.  Amino acidic scaffolds bearing unnatural side chains: an old idea generates new and versatile tools for the life sciences. , 2014, Bioorganic & medicinal chemistry letters.

[4]  Chongyang Wu,et al.  Organocatalyzed Asymmetric 1,4‐Addition of Azlactones to α,β‐Unsaturated Trichloromethyl Ketones: Synthesis of α,α‐Disubstituted α‐Amino Acid Derivatives , 2014 .

[5]  Jean Martínez,et al.  Silaproline helical mimetics selectively form an all-trans PPII helix. , 2014, Chemistry.

[6]  C. Toniolo,et al.  Solution Synthesis, Conformational Analysis, and Antimicrobial Activity of Three Alamethicin F50/5 Analogs Bearing a Trifluoroacetyl Label , 2014, Chemistry & biodiversity.

[7]  M. Kozlowski,et al.  α-Allyl-α-aryl α-Amino Esters in the Asymmetric Synthesis of Acyclic and Cyclic Amino Acid Derivatives by Alkene Metathesis , 2014, The Journal of organic chemistry.

[8]  Khoubaib Ben Haj Salah,et al.  Efficient microwave-assisted one shot synthesis of peptaibols using inexpensive coupling reagents. , 2014, Organic letters.

[9]  C. Toniolo,et al.  Multiple, consecutive, fully-extended 2.0₅-helix peptide conformation. , 2013, Biopolymers.

[10]  Jean Martínez,et al.  Synthesis of homopolypeptides with PPII structure , 2013 .

[11]  F. Cavelier,et al.  (L)-(Trimethylsilyl)alanine synthesis exploiting hydroxypinanone-induced diastereoselective alkylation , 2013, Amino Acids.

[12]  Fulin Wu,et al.  Dependence of Alamethicin Membrane Orientation on the Solution Concentration. , 2013, The journal of physical chemistry. C, Nanomaterials and interfaces.

[13]  A. Franz,et al.  Organosilicon molecules with medicinal applications. , 2013, Journal of medicinal chemistry.

[14]  T. Skrydstrup,et al.  Regioselective Rh(I)-catalyzed sequential hydrosilylation toward the assembly of silicon-based peptidomimetic analogues. , 2012, The Journal of organic chemistry.

[15]  N. Vanthuyne,et al.  Resolution of protected silaproline for a gram scale preparation , 2011, Amino Acids.

[16]  C. Bolm,et al.  Synthesis and applications of silicon-containing alpha-amino acids. , 2009, Chemical Society reviews.

[17]  Jean Martínez,et al.  α,α′‐Disubstituted Amino Acids with Silylated Side Chains as Lipophilic Building Blocks for the Synthesis of Peptaibol Analogues , 2008, Chemistry & biodiversity.

[18]  Jean Martínez,et al.  Straightforward Synthesis of Chiral Silylated Amino Acids through Hydrosilylation , 2008 .

[19]  S. Futaki,et al.  Ligand‐Induced Extramembrane Conformation Switch Controlling Alamethicin Assembly and the Channel Current , 2007, Chemistry & biodiversity.

[20]  C. Toniolo,et al.  Conformational Analysis of TOAC‐Labelled Alamethicin F50/5 Analogues , 2007, Chemistry & biodiversity.

[21]  Masakazu Tanaka.  Design and Synthesis of Chiral α,α-Disubstituted Amino Acids and Conformational Study of Their Oligopeptides , 2007 .

[22]  S. Bräse,et al.  Recent approaches towards the asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids. , 2007, Organic & biomolecular chemistry.

[23]  E. Giralt,et al.  Replacement of a proline with silaproline causes a 20-fold increase in the cellular uptake of a Pro-rich peptide. , 2006, Journal of the American Chemical Society.

[24]  J. Brunel.  Efficient method for the synthesis of an important precursor of constrained peptides. , 2005, Protein and peptide letters.

[25]  R. Tacke,et al.  The SiOH-Containing α-Amino Acid HOMe2SiCH2CH(NH2)COOH and Its Immobilization on Silica via an Si−O−Si Linkage , 2005 .

[26]  S. Sagan,et al.  Biological activity of silylated amino acid containing substance P analogues. , 2004, The journal of peptide research : official journal of the American Peptide Society.

[27]  Berk Hess,et al.  Analysis and evaluation of channel models: simulations of alamethicin. , 2002, Biophysical journal.

[28]  A. Aubry,et al.  Influence of silaproline on peptide conformation and bioactivity. , 2002, Journal of the American Chemical Society.

[29]  K. Günther,et al.  Syntheses of racemic and non-racemic silicon- and germanium-containing α-amino acids of the formula type H2NCH(CH2ElR3)COOH (El=Si, Ge; R=organyl) and incorporation of d-H2NCH(CH2SiMe3)COOH and d-H2NCH(CH2GeMe3)COOH into biologically active decapeptides: a study on C/Si/Ge bioisosterism , 2001 .

[30]  A. Aubry,et al.  A silaproline-containing dipeptide. , 2000, Acta crystallographica. Section C, Crystal structure communications.

[31]  Jean Martínez,et al.  Synthesis of Silaproline, a New Proline Surrogate , 2000 .

[32]  I. Karle,et al.  Stereochemical Analysis of Higher α,α-Dialkylglycine Containing Peptides. Characterization of Local Helical Conformations at Dipropylglycine Residues and Observation of a Novel Hydrated Multiple β-Turn Structure in Crystals of a Glycine Rich Peptide , 1997 .

[33]  C. Bevan,et al.  Chromatographic Hydrophobicity Index by Fast-Gradient RP-HPLC:  A High-Throughput Alternative to log P/log D. , 1997, Analytical chemistry.

[34]  R. Hodges,et al.  The two‐stranded α‐helical coiled‐coil is an ideal model for studying protein stability and subunit interactions , 1992, Biopolymers.

[35]  L. Kollár,et al.  Homogeneous catalytic hydrosilylation of the CC double bond in the presence of transition metalcatalysts , 1991 .

[36]  C. Toniolo,et al.  Preferred conformation of peptides from Cα,α‐symmetrically disubstituted glycines: Aromatic residues , 1991 .

[37]  V. Barone,et al.  Conformational behavior of α,α‐dialkylated peptides , 1985 .

[38]  R. Hodges,et al.  Synthesis of a model protein of defined secondary and quaternary structure. Effect of chain length on the stabilization and formation of two-stranded alpha-helical coiled-coils. , 1984, The Journal of biological chemistry.

[39]  Frederic M. Richards,et al.  A voltage-gated ion channel model inferred from the crystal structure of alamethicin at 1.5-Å resolution , 1982, Nature.

[40]  G. Jung,et al.  Conformational changes of alamethicin induced by solvent and temperature. A 13C-NMR and circular-dichroism study. , 1975, European journal of biochemistry.

[41]  C. Eaborn,et al.  The hydrogenation catalyst made from chloroplatinic acid and triethylsilane , 1969 .