Theoretical analysis of fluoroglycine conformers

Headley, Allan D.; Starnes, Stephen D.

doi:10.1002/(sici)1096-987x(20000430)21:6<426::aid-jcc2>3.0.co;2-#

Cited by 9 publications

(2 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…found in the Cambridge Structural Database System (CSDS) with dispersed FÁ Á ÁH-X angles. [59][60][61][62][63][64][65][66][67][68][69] Overall, these findings show that both desolvation of 5FU and reduced water content in the lumen of the CPNT facilitate the transport of 5FU through the CPNT.…”

Section: Fu-water Interactionsmentioning

confidence: 99%

Theoretical studies on the transport mechanism of 5-fluorouracil through cyclic peptide based nanotubes

Vijayaraj

Damme

Bultinck

et al. 2013

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

Cyclic peptide nanotubes (CPNTs) formed by the self-assembly of cyclic peptides (CPs) with an even number of alternate L/D amino acids are typically used in the field of the transport of ions and drug molecules across the lipid bilayer. This study investigates the transport mechanism of the antitumor drug molecule, 5-Fluorouracil (5FU), through the CPNT using classical and steered molecular dynamics simulations combined with umbrella sampling.During the transport of 5FU through the CPNT, 5FU is partially desolvated because the lumen of the CPNT is too small to allow for water molecules solvating it. 5FU forms Hbonding interactions with the backbones of CPNT and at the same time, also forms hydrophobic contacts with the backbone Cα and C atoms of CPNT. The cooperative breaking of the H-bond and hydrophobic interactions between CPNT and 5FU increases the pulling force to transport the 5FU from the mid-Cα region to the Cα one. The calculated free energies of binding reveal that the energy barriers for the transport of 5FU are ~ -6.0 and ~ -2.0 kcal/mol in the mid-Cα and Cα plane regions, respectively.

show abstract

Section: Fu-water Interactionsmentioning

confidence: 99%

Theoretical studies on the transport mechanism of 5-fluorouracil through cyclic peptide based nanotubes

Vijayaraj

Damme

Bultinck

et al. 2013

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

show abstract

“…Fluorinated derivatives of amino acids are assuming increasing importance as probes of biological function and enzyme mechanism, particularly because the electron-withdrawing effects of fluorine substituents often have profound effects on reactivity and conformational preferences. , For example, fluorinated analogues of glutamic acid possess antitumor activity and are modulators of folate poly-γ-glutamate biosynthesis . Our interest in fluorinated amino acids has been stimulated by our recent efforts to characterize the structure and mechanism of asparagine synthetase (AS), a glutamine-dependent amidotransferase that appears to be intimately linked with progression through the cell cycle and cellular responses to amino acid starvation .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of l-4,4-Difluoroglutamic Acid via Nucleophilic Addition to a Chiral Aldehyde

et al. 2001

View full text Add to dashboard Cite

Fluorine-containing derivatives of amino acids are assuming increasing importance as probes of biological function and enzyme mechanism. We now report a new, flexible route to enantiomerically pure L-4,4-difluoroglutamic acid that exploits the addition of difluorinated nucleophiles to configurationally stable alpha-aminoaldehydes. Conversion of the difluorinated adducts to L-4,4-difluoroglutamic acid can be accomplished in three steps by Barton-McCombie dehydroxylation and acid hydrolysis.

show abstract

Hyperconjugation Contributes to the Bimodal Distribution of Glycine Conformations Observed in Protein Three‐Dimensional Structures

2011

View full text Add to dashboard Cite

Unravelling the mystery of protein folding has been a primary goal of the biological sciences since Anfinsen's seminal experiments demonstrated the connection between a protein's amino acid sequence and its active three-dimensional conformation.[1] Since then, there has been steady progress in the experimental, [2] theoretical, [3] analytical [4] and predictive [5] aspects of the protein folding problem. However, the matter is far from resolved, [6] remaining one of the great open problems of our time. [7] A complete understanding of the forces acting on individual amino acids during folding would undoubtedly enhance our understanding of this fundamental process.One of the more pivotal amino acids for protein folding and three-dimensional structure is glycine: H 2 NCH 2 COOH. Lacking a side chain, this residue is capable of adopting many conformations that are sterically challenging for amino acids with larger side chains. Theoretical investigations of glycine conformations have focused on isolated glycine molecules in the gas phase, [8] with most reports maintaining that hydrogen bonding between the amine and carboxylic acid moieties is responsible for the preferred gas-phase planar geometries.[8a, d-h, j] The conformational preferences of glycine in the context of a folded protein, on the other hand, have received far less attention. The original Ramachandran plot for glycine, based on hardsphere steric repulsions, suggested that most of the (f,y) conformational space apart from the two axes (f= 0, y = 0) should be available to glycine, [9] but as the number of determined high-resolution protein structures has grown, a clear bimodal distribution of preferred (f,y) conformations, characterized by y = 08 AE 508 and y = 1808 AE 608, has emerged (Figure 1). Ho and Brasseur have recently analysed the discrepancy between theoretical and actual glycine conformational density and concluded that this bimodal distribution is a result of steric clashes between glycine a H i atoms and nearby O i and N i+1 atoms. [10] Our interest in glycine stems from a little-heralded observation about the frequency of glycine-proline (Gly-Pro) pairings at the C termini (CT) of helices. Gunasekaran et al. report that out of the 318 helices ending with a glycine in a left-handed helical (a L ) conformation in their dataset, none was found to have a proline immediately following the capping glycine, despite proline's predominance in this second capping position.[11] The authors attributed this curious finding to the inability of proline to form an amide hydrogen bond characteristic of a L -capped helices.[11] These findings appear to be a special case of a more widespread phenomenon reported two decades ago, in which no glycine residues were found to adopt the a L conformation when followed by a proline, regardless of secondary structural environment. [12] This phenomenon was attributed to a steric clash between Gly NH and Pro d CH 2 atoms. [12] In this work we re-examine the conformational preferences of glycine and the instances of ...

show abstract

Theoretical analysis of fluoroglycine conformers

Cited by 9 publications

References 41 publications

Theoretical studies on the transport mechanism of 5-fluorouracil through cyclic peptide based nanotubes

Theoretical studies on the transport mechanism of 5-fluorouracil through cyclic peptide based nanotubes

Synthesis of l-4,4-Difluoroglutamic Acid via Nucleophilic Addition to a Chiral Aldehyde

Hyperconjugation Contributes to the Bimodal Distribution of Glycine Conformations Observed in Protein Three‐Dimensional Structures

Contact Info

Product

Resources

About