Probing Functional Heteromeric Chemokine Protein–Protein Interactions through Conformation‐Assisted Oxime Ligation

Protein–protein interactions (PPIs) govern most processes in living cells. Current drug development strategies are aimed at disrupting or stabilizing PPIs, which require a thorough understanding of PPI mechanisms. Examples of such PPIs are heteromeric chemokine interactions that are potentially involved in pathological disorders such as cancer, atherosclerosis, and HIV. It remains unclear whether this functional modulation is mediated by heterodimer formation or by the additive effects of mixed chemokines on their respective receptors. To address this issue, we report the synthesis of a covalent RANTES‐PF4 heterodimer (termed OPRAH) by total chemical synthesis and oxime ligation, with an acceleration of the final ligation step driven by PPIs between RANTES and PF4. Compared to mixed separate chemokines, OPRAH exhibited increased biological activity, thus providing evidence that physical formation of the heterodimer indeed mediates enhanced function.     

Der Zerfall des Se71

The present paper starts form the original Ginzburg-Landau-equations of superconductivity and the linear theory of elasticity for internal stresses as well as the experimental fact that the specific volume and the elastic constants vary throughout the superconducting phase. With the aid of phenomenological expressions for the free energy and the spontaneous deformation (superconductive magnetostriction) of a deformable type II superconductor, a general method is given for the determination of the interaction between the field of the order parameter, the magnetic field, and the field of the elastic deformations. For an isolated straight vortex-line and for a straight vortex-line in the neighbourhood of a dislocation of arbitrary character, formulas for the internal stresses are derived using first order perturbation theory (corresponding to first powers in the changes of specific volume and elastic constants).