Polyphosphates and Pyrophosphates of Pentopyranoses and Pentofuranoses as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Oxygen Release

Fylaktakidou, Konstantina C.; Duarte, Carolina D.; Jogireddy, Rajamalleswaramma; Koumbis, Alexandros E.; Nicolau, Claude; Lehn, Jean‐Maríe

doi:10.1002/cmdc.201100110

Cited by 4 publications

(1 citation statement)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hemoglobin also binds antisickling compounds such as clofibric acid and bezafibrate within the central cavity bound at sites approximately 20Å away from the binding site of DPG but which have additive effects on the binding of DPG. Sites located at the boundary between subunits in the axial cavity constitute a novel category of sites important for drug design (59), and they are associated exclusively with the oligomeric organization of the protein. There are many additional examples of sites located at subunit boundaries in regulatory enzymes.…”

Section: Sites At Subunit Boundariesmentioning

confidence: 99%

Allostery and the Monod-Wyman-Changeux Model After 50 Years

Changeux

2012

Annu. Rev. Biophys.

339

314

View full text Add to dashboard Cite

The Monod-Wyman-Changeux (MWC) model was conceived in 1965 to account for the signal transduction and cooperative properties of bacterial regulatory enzymes and hemoglobin. It was soon extended to pharmacological receptors for neurotransmitters and other macromolecular entities involved in intracellular and intercellular communications. Five decades later, the two main hypotheses of the model are reexamined on the basis of a variety of regulatory proteins with known X-ray structures: (a) Regulatory proteins possess an oligomeric structure with symmetry properties, and (b) the allosteric interactions between topographically distinct sites are mediated by a conformational transition established between a few preestablished states with conservation of symmetry and ligand-directed conformational selection. Several well-documented examples are adequately represented by the MWC model, yet a few possible exceptions are noted. New questions are raised concerning the dynamics of the allosteric transitions and more complex supramolecular ensembles.

show abstract

Section: Sites At Subunit Boundariesmentioning

confidence: 99%

Allostery and the Monod-Wyman-Changeux Model After 50 Years

Changeux

2012

Annu. Rev. Biophys.

339

314

View full text Add to dashboard Cite

show abstract

Tetrakisphosphates and Bispyrophosphates of myo‐Inositol Derivatives as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Oxygen Release

Koumbis¹,

Duarte²,

Nicolau³

et al. 2010

ChemMedChem

View full text Add to dashboard Cite

Various 2,5- and 1,4-substituted and unsubstituted myo-inositol tetrakisphosphates and bispyrophosphates were prepared following a general synthetic pathway. All final compounds were tested for their capability to induce oxygen release from human hemoglobin. Most of these proved to be efficient allosteric effectors, with similar affinities for hemoglobin to that of myo-inositol hexakisphosphate, which is one of the best known allosteric effectors of hemoglobin. The efficacy was found to be higher for free phosphates than pyrophosphates. As allosteric Hb effectors, these compounds enable enhanced oxygen release. These effects increase with the strength of Hb binding and correspond primarily to electrostatic interactions. Stereochemical and steric factors also play a significant but secondary role in molecular recognition. In view of the central role played by hypoxia in numerous types of diseases, the exploration of myo-inositol phosphate derivatives represents an important avenue in the search for substances which act on the oxygenation status of tissues and may have significant potential in the discovery and development of novel drug candidates.

show abstract

Versatile Synthesis of 1‐O‐(ω‐Aminolauryl)‐I(4,5)P₂

Varvogli¹,

Fylaktakidou²,

Farmaki³

et al. 2012

Eur J Org Chem

Self Cite

View full text Add to dashboard Cite

The synthesis of a model 1‐O‐(ω‐aminoacyl)‐IP2 derivative, lauryl 4,5‐bisphosphate 31, was realized following a versatile and high‐yielding scheme. The flexible synthetic strategy used for this purpose allows the preparation of a range of other useful IP, IP2 and IP3 derivatives. In view of the central role played by IPs and PIPs in cellular life, the preparation of functionalized myo‐inositol derivatives of this type may facilitate the isolation and fluorescent localization of related proteins.

show abstract

Polyphosphates and Pyrophosphates of Pentopyranoses and Pentofuranoses as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Oxygen Release

Cited by 4 publications

References 62 publications

Allostery and the Monod-Wyman-Changeux Model After 50 Years

Allostery and the Monod-Wyman-Changeux Model After 50 Years

Tetrakisphosphates and Bispyrophosphates of myo‐Inositol Derivatives as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Oxygen Release

Versatile Synthesis of 1‐O‐(ω‐Aminolauryl)‐I(4,5)P₂

Contact Info

Product

Resources

About

Polyphosphates and Pyrophosphates of Pentopyranoses and Pentofuranoses as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Oxygen Release

Cited by 4 publications

References 62 publications

Allostery and the Monod-Wyman-Changeux Model After 50 Years

Allostery and the Monod-Wyman-Changeux Model After 50 Years

Tetrakisphosphates and Bispyrophosphates of myo‐Inositol Derivatives as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Oxygen Release

Versatile Synthesis of 1‐O‐(ω‐Aminolauryl)‐I(4,5)P2

Contact Info

Product

Resources

About

Versatile Synthesis of 1‐O‐(ω‐Aminolauryl)‐I(4,5)P₂