Nanomolar binding of peptides containing noncanonical amino acids by a synthetic receptor

This paper describes the molecular recognition of phenylalanine derivatives and their peptides by the synthetic receptor cucurbit[7]uril (Q7). The 4-tert-butyl and 4-aminomethyl derivatives of phenylalanine (tBuPhe and AMPhe) were identified from a screen to have 20-30-fold higher affinity than phenylalanine for Q7. Placement of these residues at the N-terminus of model tripeptides (X-Gly-Gly), resulted in no change in affinity for tBuPhe-Gly-Gly, but a remarkable 500-fold increase in affinity for AMPhe-Gly-Gly, which bound to Q7 with an equilibrium dissociation constant (K(d)) value of 0.95 nM in neutral phosphate buffer. Structure-activity studies revealed that three functional groups work in a positively cooperative manner to achieve this extraordinary stability (1) the N-terminal ammonium group, (2) the side chain ammonium group, and (3) the peptide backbone. Addition of the aminomethyl group to Phe substantially improved the selectivity for peptide versus amino acid and for an N-terminal vs nonterminal position. Importantly, Q7 binds to N-terminal AMPhe several orders of magnitude more tightly than any of the canonical amino acid residues. The high affinity, single-site selectivity, and small modification in this system make it attractive for the development of minimal affinity tags.     

On Optimum Propulsion by Means of Small Periodic Motions of a Rigid Profile. I. Properties of Optimum Motions

The problem of optimum thrust generation by means of a rigid profile performing small arbitrarily periodic motions in an inviscid incompressible fluid is studied. The motions considered have to generate a prescribed mean value of thrust and must be such that the contribution to this mean thrust by the suction at the leading edge does not exceed a certain given value. Furthermore, the motions are in general subjected to a maximum type constraint on their amplitude. For this infinite dimensional, nonconvex and nonsmooth optimization problem, a generalized Lagrange multiplier rule is derived. In case the constraint on the amplitude is omitted, the optimum motions are calculated analytically; for the general case a number of properties of the solutions are derived from the Lagrange multiplier rule.     

Eine einfache diastereoselektive synthese von (1sr,3sr,5sr)-2-azabicyclo [3.3.0] Octan-3-carbonsäure

(1SR,3SR,5SR)-2-Azabicyclo [3.3.0] octane-3-carboxylic acid, precursor of the angiotensin-converting-enzyme inhibitor Hoe 498, is easily prepared from 1-chloro-1-cyclopentene-2-carbaldehyde in three steps.     

Numerical simulation of QCD with u,d, s and c quarks in the twisted-mass Wilson formulation

A first study of numerical Monte Carlo simulations with two quark doublets, a mass-degenerate one and a mass-split one, interpreted as u, d, s and c quarks, is carried out in the framework of the twisted mass Wilson lattice formulation. Tuning the bare parameters of this theory is explored on 12³·24 and 16³·32 lattices at lattice spacings a≃0.20 fm and a≃0.15 fm, respectively.