146398-18-7Relevant articles and documents
Protein-protein interface mimicry by an oxazoline piperidine-2,4-dione
Li, Xun,Taechalertpaisarn, Jaru,Xin, Dongyue,Burgess, Kevin
supporting information, p. 632 - 635 (2015/03/05)
Representative minimalist mimics 1 were prepared from amino acids. Scaffold 1 was not designed to mimic any particular secondary structure, but simulated accessible conformations of this material were compared with common ideal secondary structures and with >125000 different protein-protein interaction (PPI) interfaces. This data mining exercise indicates that scaffolds 1 can mimic features of sheet-turn-sheets, somewhat fewer helical motifs, and numerous PPI interface regions that do not resemble any particular secondary structure.
A multifaceted secondary structure mimic based on piperidine-piperidinones
Xin, Dongyue,Perez, Lisa M.,Ioerger, Thomas R.,Burgess, Kevin
, p. 3594 - 3598 (2014/04/17)
Minimalist secondary structure mimics are typically made to resemble one interface in a protein-protein interaction (PPI), and thus perturb it. We recently proposed suitable chemotypes can be matched with interface regions directly, without regard for secondary structures. Here we describe a modular synthesis of a new chemotype 1, simulation of its solution-state conformational ensemble, and correlation of that with ideal secondary structures and real interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are quite separated from each other, in orientations that closely resemble ideal sheet or helical structures, similar non-ideal structures at PPI interfaces, and regions of other PPI interfaces where the mimic conformation does not resemble any secondary structure. 68 different PPIs where conformations of 1 matched well were identified. A new method is also presented to determine the relevance of a minimalist mimic crystal structure to its solution conformations. Thus dld-1-faf crystallized in a conformation that is estimated to be 0.91 kcal-mol-1 above the minimum energy solution state. Do we know, when designing a new peptidomimetic scaffold like the one shown, how it can resemble secondary structures? Design and modular synthesis of this elongated mimic is reported, and the structure is related to ideal and real structures at PPI interfaces.
Synthesis and conformation of fluorinated β-peptidic compounds
Peddie, Victoria,Butcher, Raymond J.,Robinson, Ward T.,Wilce, Matthew C. J.,Traore, Daouda A. K.,Abell, Andrew D.
, p. 6655 - 6662 (2012/07/28)
Experimental and theoretical data indicate that, for α-fluoroamides, the F-C-C(O)-N(H) moiety adopts an antiperiplanar conformation. In addition, a gauche conformation is favoured between the vicinal C-F and C-N(CO) bonds in N-β-fluoroethylamides. This study details the synthesis of a series of fluorinated β-peptides (1-8) designed to use these stereoelectronic effects to control the conformation of β-peptide bonds. X-ray crystal structures of these compounds revealed the expected conformations: with fluorine β to a nitrogen adopting a gauche conformation, and fluorine α to a C=O group adopting an antiperiplanar conformation. Thus, the strategic placement of fluorine can control the conformation of a β-peptide bond, with the possibility of directing the secondary structures of β-peptides. Copyright
Succinct synthesis of β-amino acids via chiral isoxazolines
Fuller, Amelia A.,Chen, Bin,Minter, Aaron R.,Mapp, Anna K.
, p. 5376 - 5383 (2007/10/03)
β-Amino acids are important synthetic targets due to their presence in a wide variety of natural products, pharmaceutical agents, and mimics of protein structural motifs. While β-amino acids containing geminal substitution patterns have enormous potential for application in these contexts, synthetic challenges to the stereoselective preparation of this class of compound have thus far limited more complete studies. We present here a straightforward method employing chiral isoxazolines as key intermediates to access five different β-amino acid structural types with excellent selectivity. Of particular note is the use of this approach to prepare highly substituted cis-β-proline analogues. The ready access to these diversely substituted compounds is expected to facilitate future studies of the structure and function of this important class of molecules.
Catalytic enantioselective conjugate addition of carbamates
Palomo, Claudio,Oiarbide, Mikel,Halder, Rajkumar,Kelso, Michael,Gomez-Bengoa, Enrique,Garcia, Jesus M.
, p. 9188 - 9189 (2007/10/03)
Catalytic, asymmetric conjugate addition of carbamates to enoyl systems has been realized for the first time, providing a two-step access to virtually enantiopure N-protected β-amino acids. Copyright
A concise approach to structurally diverse β-amino acids
Minter, Aaron R.,Fuller, Amelia A.,Mapp, Anna K.
, p. 6846 - 6847 (2007/10/03)
We have demonstrated that the high yields and selectivities of 1,3-dipolar cycloadditions can be translated into facile stereoselective syntheses of a diverse array of β-amino acids, key components of bioactive natural products, β-lactams, and peptidomimetics. Simply by selecting different combinations of three readily available starting materials (an oxime, a chiral allylic alcohol, and a nucleophile), we used the reaction sequence to prepare four different β-amino acid structural types with a variety of substitution patterns in good overall yield. Of particular note is the use of this approach to prepare highly substituted β-amino acids not readily accessible by previously reported methodologies. This will pave the way for future studies of the structure and function of this important class of molecules. Copyright
β-hairpins generated from hybrid peptide sequences containing both α- and β-amino acids
Gopi, Hosahudya N.,Roy, Rituparna S.,Raghothama, Srinivasa R.,Karle, Isabella L.,Balaram, Padmanabhan
, p. 3313 - 3330 (2007/10/03)
The incorporation of the β-amino acid residues into specific positions in the strands and β-turn segments of peptide hairpins is being systematically explored, The presence of an additional torsion variable about the C(α)-C(β) bond (θ) enhances the confor
Synthesis of optically active β-amino acid N-carboxyanhydrides
Cheng, Jianjun,Ziller, Joseph W.,Deming, Timothy J.
, p. 1943 - 1946 (2007/10/03)
(Equation presented) Methodology has been developed for the general synthesis of optically active β-amino acid N-carboxyanhydrides (β-NCAs) through cyclization of Nβ-Boc or Nβ-Cbz β-amino acids using phosphorus tribromide. The format
α-Oxymethyl ketone enolates for the asymmetric Mannich reaction. From acetylene and N-alkoxycarbonylimines to β-amino acids
Palomo, Claudio,Oiarbide, Mikel,Gonzalez-Rego, M. Concepcion,Sharma, Arun K.,Garcia, Jesus M.,Gonzalez, Alberto,Landa, Cristina,Linden, Anthony
, p. 1063 - 1066 (2007/10/03)
The insufficient diastereoselectivity and generality, which are the main problems of the 'acetate' aza - aldol reaction, can now be addressed through the reaction of the lithium enolate of endo-O-trimethylsilyl acetyl isoborneol with various N[(p-tolylsul
