Bimetallic Rod-Packing Metal–Organic Framework Combining Two Charged Forms of 2-Hydroxyterephthalic Acid

Although many rod-packing metal-organic frameworks are known, few are based on ordered heterometallic rod building unit. We show here the synthesis of CPM-76 based on an unprecedented Zn-Mg bimetallic rod with crystallographically distinguishable metal sites. The configuration of the rod offers two types of coordination site with trigonal bipyramidal and octahedral sites selectively occupied by Zn and Mg, respectively. Also unusual is the inter-connection mode between the rods, which is based on dual-charged forms (−3 and −2) of the 2-hydroxyterephthalic acid (H₃OBDC) ligand. Interestingly, each metal site in CPM-76 binds one solvent molecule, leading to a high density of solvent binding sites.     

Stereocontrolled protein surface recognition using chiral oligoamide proteomimetic foldamers

The development of foldamers capable of selective molecular recognition of solvent exposed protein surfaces represents an outstanding challenge in supramolecular chemical biology. Here we introduce an oligoamide foldamer with well-defined conformation that bears all the hallmarks of an information rich oligomer. Specifically, the foldamer recognizes its target protein hDM2 leading to inhibition of its protein–protein interaction with p53 in a manner that depends upon the composition, spatial projection and stereochemistry of functional groups appended to the scaffold. Most significantly, selective inhibition of p53/hDM2 can be achieved against four other targets and the selectivity for p53/hDM2 inhibition versus Mcl-1/NOXA-B inhibition is critically dependent upon the stereochemistry of the helix mimetic.     

Variable-Length Ester-Based Staples for α-Helical Peptides by Using A Double Thiol-ene Reaction

A novel peptide stapling method effected by a double thiol-ene reaction between two cysteine residues and a divinyl diester to access stapled peptides with enhanced cell permeability is reported. This diverse chemical tool kit provides facile access to stapled peptides with varying bridge lengths. Stapled Axin mimetics were synthesised by using this stapling method resulting in improved α-helicity relative to the unstapled peptide. Cell penetrating stapled analogues of the SIGK peptide that targets the protein–protein interaction hotspot of Gβγ proteins were also synthesised that exhibited a moderate increase in α-helicity and were cell permeable. This chemoselective peptide stapling method is highly amenable as a facile method to easily modify synthetic α-helical peptides to target intracellular proteins.     

Direct Leuckart-type reductive amination of aldehydes and ketones: a facile one-pot protocol for the preparation of secondary and tertiary amines

A high-yielding and facile one-pot Leuckart-type reaction for rapid access to a number of 2° and 3° amines is described.     

Stabilization of non-homogeneous elastic materials with voids

We study the asymptotic behavior of the solution of the non-homogeneous elastic system with voids and a thermal effect. We first prove the well-posedness of this system under some realistic assumptions on the coefficients. Since this system suffers of exponential stability (as shown in dimension 1 in Pamplona, Muñoz Rivera, and Quintanilla (2009) [18]), our main results concern strong and polynomial stabilities again under some assumptions on the coefficients. These stabilities are obtained in a closed subspace of the natural Hilbert space. Hence we characterize its orthogonal and further show that in the whole space the energy tends strongly or polynomially to the energy of the projection of the initial datum on this orthogonal space. In this respect we extend and precise former results obtained in one dimension in Pamplona, Muñoz Rivera, and Quintanilla (2009) [18].     

Evaluation of log P,pKa, and log D predictions from the SAMPL7 blind challenge

Journal of Computer-Aided Molecular Design - The Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) challenges focuses the computational modeling community on areas in need of...