University of Southampton

About: University of Southampton is a education organization based out in Southampton, United Kingdom. It is known for research contribution in the topics: Population & Laser. The organization has 37184 authors who have published 99400 publications receiving 3462915 citations. The organization is also known as: Southampton University & Soton Uni.

Targeting C-reactive protein for the treatment of cardiovascular disease

Abstract: Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement1, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively2, 3. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement4. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP2, 3. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.

Structural and molecular recognition studies with acyclic anion receptors

Abstract: Acyclic molecules containing amides, ureas, and pyrrole groups have proven to be effective and selective anion-binding agents. In this Account, the structural chemistry of isophthalamide anion complexes, ortho-phenylenediamine based bis-ureas, and amidopyrroles, as well as anion-triggered deprotonation processes in neutral anion receptor systems, are discussed.

Toroidal Dipolar Response in a Metamaterial

Abstract: Toroidal multipoles are fundamental electromagnetic excitations different from those associated with the familiar charge and magnetic multipoles. They have been held responsible for parity violation in nuclear and particle physics, but direct evidence of their existence in classical electrodynamics has remained elusive. We report on the observation of a resonant electromagnetic response in an artificially engineered medium, or metamaterial, that cannot be attributed to magnetic or charge multipoles and can only be explained by the existence of a toroidal dipole. Our direct experimental evidence of the toroidal response brings attention to the often ignored electromagnetic interactions involving toroidal multipoles, which could be present in naturally occurring systems, especially at the macromolecule level, where toroidal symmetry is ubiquitous.