Using Gas-Phase Guest–Host Chemistry to Probe the Structures of b Ions of Peptides

Middle-sized b _n (n????5) fragments of protonated peptides undergo selective complex formation with ammonia under experimental conditions typically used to probe hydrogen?Cdeuterium exchange in Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Other usual peptide fragments like y, a, a*, etc., and small b _n (n????4) fragments do not form stable ammonia adducts. We propose that complex formation of b _n ions with ammonia is characteristic to macrocyclic isomers of these fragments. Experiments on a protonated cyclic peptide and N-terminal acetylated peptides fully support this hypothesis; the protonated cyclic peptide does form ammonia adducts while linear b _n ions of acetylated peptides do not undergo complexation. Density functional theory (DFT) calculations on the proton-bound dimers of all-Ala b ₄ , b ₅ , and b ₇ ions and ammonia indicate that the ionizing proton initially located on the peptide fragment transfers to ammonia upon adduct formation. The ammonium ion is then solvated by N⁺-H??O H-bonds; this stabilization is much stronger for macrocyclic b _n isomers due to the stable cage-like structure formed and entropy effects. The present study demonstrates that gas-phase guest?Chost chemistry can be used to selectively probe structural features (i.e., macrocyclic or linear) of fragments of protonated peptides. Stable ammonia adducts of b ₉ , b ₉ -A, and b ₉ -2A of A₈YA, and b ₁₃ of A₂₀YVFL are observed indicating that even these large b-type ions form macrocyclic structures.     

Bigger data,collaborative tools and the future of predictive drug discovery

Over the past decade we have seen a growth in the provision of chemistry data and cheminformatics tools as either free websites or software as a service commercial offerings. These have transformed how we find molecule-related data and use such tools in our research. There have also been efforts to improve collaboration between researchers either openly or through secure transactions using commercial tools. A major challenge in the future will be how such databases and software approaches handle larger amounts of data as it accumulates from high throughput screening and enables the user to draw insights, enable predictions and move projects forward. We now discuss how information from some drug discovery datasets can be made more accessible and how privacy of data should not overwhelm the desire to share it at an appropriate time with collaborators. We also discuss additional software tools that could be made available and provide our thoughts on the future of predictive drug discovery in this age of big data. We use some examples from our own research on neglected diseases, collaborations, mobile apps and algorithm development to illustrate these ideas.     

A note on the Newton radius

The Newton radius of a code is the largest weight of a uniquely correctable error. We establish a lower bound for the Newton radius in terms of the rate. In particular we show that in any family of linear codes of rate below one half, the Newton radius increases linearly with the codeword length.     

The effect of clay on the morphology of multiphase latex particles

The effect of montmorrilonite clay (MMT) platelets on the morphology of polystyrene/poly(methyl methacrylate) (PMMA) composite latex particles prepared via PMMA-seeded (semi-) batch emulsion polymerization of styrene was studied. It was found that the particle morphology obtained greatly depended on the ability of the clay platelets to diffuse through the polymer particle. Indeed, when the reactions were strictly under kinetic control, i.e., where the clay platelets were unable to diffuse during polymerization, anisotropic core-shell-like morphologies with split core were observed. A better mobility of the clay platelets could more or less restrict the diffusion of the second-stage polymers within the host polymer, leading to original kinetically controlled morphologies. In the case of a full migration of the clay platelets to the particle surface, the penetration of the second-stage polymer species in the seed latex was found to be more limited, enhancing the formation of secondary particles.     

Highly Enantioselective,Organocatalytic, and Scalable Synthesis of a Rare cis,cis-Tricyclic Diterpenoid

A highly enantioselective, organocatalytic, and scalable synthesis of a very unusual cis-decalin-cis-hydrindane tricyclic diterpenoid system has been achieved. Despite the prevalent pharmacological space that the related trans,trans and trans,cis-systems occupy, there have been no reports of an asymmetric synthesis of the cis,cis systems in the literature until now. We demonstrate the flexibility of our approach not only through access to a diverse range of products, all of which are attained in exceptionally high selectivities, but also by showing their easy conversion to the corresponding trans,cis-system and other derivatives.     

A-posteriori KAM theory with optimal estimates for partially integrable systems

In this paper we present a-posteriori KAM results for existence of d-dimensional isotropic invariant tori for n-DOF Hamiltonian systems with additional $n?d$ independent first integrals in involution. We carry out a covariant formulation that does not require the use of action-angle variables nor symplectic reduction techniques. The main advantage is that we overcome the curse of dimensionality avoiding the practical shortcomings produced by the use of reduced coordinates, which may cause difficulties and underperformance when quantifying the hypotheses of the KAM theorem in such reduced coordinates. The results include ordinary and (generalized) iso-energetic KAM theorems. The approach is suitable to perform numerical computations and computer assisted proofs.