Increasing oxygen delivery: Allosteric effectors of human hemoglobin

December 23, 2010

(PhysOrg.com) -- Numerous diseases, such as cardiovascular ailments and cancer, are characterized by a lack of oxygen in specific tissues. Therefore, increasing the supply of oxygen delivered by red blood cells (RBCs) to counteract the effects of hypoxia has much potential therapeutic interest. Nobel laureate Jean-Marie Lehn and colleagues at the Université de Strasbourg (France) have undertaken a series of collaborative research efforts to address this.

Oxygen release from (Hb) is regulated in humans by the allosteric effector 2,3-bisphosphoglycerate (2,3-BPG). Increased oxygen release may in principle be achieved by a more powerful effector molecule that would bind Hb, shift its oxygenation curve, and be able to cross the RBC plasma membrane. It was discovered earlier that myo-inositol trispyrophosphate (ITPP) is such a molecule, and is able to markedly increase oxygen delivery by RBCs both ex vivo and in vivo.

It is now found (ChemBioChem, referenced below) that ITPP entry into RBCs is mediated by the anion transporter Band 3 protein and may be suppressed by specific inhibition of this carrier. As Band 3 is mainly localized in the RBC membrane, the uptake of ITPP is highly specific towards RBCs, a feature of major importance for its potential medical use. The therapeutic value of such effector molecules warrants a broad exploration of the chemical space, involving both molecular recognition of the allosteric pocket of Hb and oxygen release from Hb.

The synthesis of a number of phosphorylated derivatives of hexapyranoses (ChemMedChem, DOI: 10.1002/cmdc.201000366) and of selectively substituted myo-inositol derivatives (ChemMedChem, DOI: 10.1002/cmdc.201000421), together with the investigation of their effect on oxygen release from pure Hb allow the exploration of structure-activity relationships for various molecular features (such as charge and shape) and provides information about the design of allosteric effectors of Hb as potential drugs that present a wide range of activities.

Explore further: Experimental anti-cancer synthetic molecule targets tumor cell growth and angiogenesis

More information: Jean-Marie Lehn, myo-Inositol Trispyrophosphate: A Novel Allosteric Effector of Hemoglobin with High Permeation Selectivity across the Red Blood Cell Plasma Membrane, ChemBioChem 2010, 11, No. 18, 2543–2548, dx.doi.org/10.1002/cbic.201000499

Related Stories

Anticancer drugs might be of benefit to sickle-cell patients

December 6, 2007

Sickle cell disease (SCD) is an inherited blood disorder caused by a genetic mutation that leads to the generation of a mutant form of the beta-globin chain of hemoglobin (Hb). Red blood cells containing Hb with this mutant ...

Genetic signature predicts outcome of pediatric liver cancer

December 8, 2008

Scientists have identified a genetic signature that is remarkably effective at predicting the prognosis of an aggressive liver cancer in children. The research, published by Cell Press in the December issue of the journal ...

Recommended for you

Cloud formation—how feldspar acts as ice nucleus

December 9, 2016

In the atmosphere, feldspar particles act as ice nuclei that make ice crystals grow in clouds and enable precipitation. The discovery was made by researchers of Karlsruhe Institute of Technology (KIT) and University College ...

Why cryptophyte algae are really good at harvesting light

December 8, 2016

In an algae-eat-algae world, it's the single-celled photosynthetic organisms at the top (layer of the ocean) that absorb the most sunlight. Underneath, in the sublayers, are cryptophyte algae that must compete for photons ...

Chemical trickery corrals 'hyperactive' metal-oxide cluster

December 8, 2016

After decades of eluding researchers because of chemical instability, key metal-oxide clusters have been isolated in water, a significant advance for growing the clusters with the impeccable control over atoms that's required ...

Oxygen can wake up dormant bacteria for antibiotic attacks

December 8, 2016

Bacterial resistance does not come just through adaptation to antibiotics, sometimes the bacteria simply go to sleep. An international team of researchers is looking at compounds that attack bacteria's ability to go dormant ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Ratfish
not rated yet Dec 23, 2010
The Tour de France competitors anxiously await these drugs.
CarolinaScotsman
not rated yet Dec 24, 2010
The Tour de France competitors anxiously await these drugs.

So do those of us with congestive heart failure.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.