Energy minimization of rigid-geometry polypeptides with exactly closed disulfide loops

A method has been developed for minimizing the energy of a polypeptide with rigid geometry while keeping all disulfide loops closed exactly. Exact closure of disulfide loops implies that some dihedral angles become implicit functions of the remaining dihedral angles in the polypeptide; the efficacy of the method is related to the manner in which the implicitly defined dihedral angles are chosen. The method has been used to find minimum-energy conformations of bovine pancreatic trypsin inhibitor, ribonuclease A, crambin, the defensin HNP3 dimer, and ω-conotoxin. For the first two proteins, the starting conformations for energy minimization had been derived previously from crystal structures using pseudopotentials to keep the disulfide loops almost closed. Starting conformations for the remaining three proteins were derived from their crystal or NMR structures by similar procedures. In all cases, the energy-minimized structures had a significantly and, in some cases, substantially, lower energy than the starting structures. The RMS deviations between the exactly closed energy- minimized structures and the crystal or NMR structures from which they were derived ranged from 0.9 Å to 1.9 Å, suggesting that the computed structures can serve as “regularized” native structures for these proteins. The energy of a ribonuclease derivative lacking the 65–72 disulfide bridge was minimized using the procedure; the result showed that this derivative has a low-energy structure with a conformation very close to that of native ribonuclease, and is consistent with its postulated role in the folding of ribonuclease. These results offer strong support for the validity of the rigid-geometry model in the studies of the conformational energy of proteins. © 1997 by John Wiley & Sons, Inc.     

Synthesis and properties of stereoregular fluoro-polymers via ring-opening metathesis polymerization of fluorinated norbornenes and norbornadienes. An overview and progress report

Since the first report of the ring-opening metathesis polymerization of fluorinated monomers in 1979 considerable advances in precision and control of such syntheses have been achieved through the introduction of well defined initiators. It is now possible to carry out well controlled living and stereoregular polymerizations. The products of such syntheses can display unusually high relaxed dielectric constants, an observation which is crucial to the assignment of their tacticities and probably significant with regard to possible applications of this type of material.     

Controlled polymerization of lactides at ambient temperature using [5-Cl-salen]AlOMe

The Schiff-base aluminium complex [5-Cl-salen]AlOMe ( 2 ) is shown to be a room temperature initiator for controlled ring-opening polymerization of D ,L - and L -lactides; the molecular structure of the precursor [5-Cl-salen]AlMe ( 1 ) reveals a distorted trigonal bipyramidal geometry.     

Acylphosphonamidates and α-hydroxyiminophosphonamidates. Synthesis of N-acylphosphordiamidates by Beckmann rearrangement. Crystal structure of (E)-α-hydroxyiminobenzyl-1-pyrrolidinylphosphinate

Reaction of methyl benzoylphosphonochloridate (3) with a secondary or primary series of amines yielded methyl benzoylphosphonamidates, 4a-e. The latter compounds reacted with hydroxylamine to yield a-hydroxyiminobenzylphosphonamidates (5a-e), largely as (E)-isomers. The structure of methyl (E)-a-hydroxyimino-benzyl-1-pyrrolidinylphosphinate (5b) was determined by single-crystal X-ray crystallography. Heating oximes 5a-e in boiling toluene caused them to undergo Beckmann rearrangement to N-benzoylphosphordiamidates 6a-e. © 1996 John Wiley & Sons, Inc.     

Apolipoprotein E Recognizes Alzheimer's Disease Associated 3-O Sulfation of Heparan Sulfate

Apolipoprotein E (ApoE)’s ϵ4 alle is the most important genetic risk factor for late onset Alzheimer's Disease (AD). Cell-surface heparan sulfate (HS) is a cofactor for ApoE/LRP1 interaction and the prion-like spread of tau pathology between cells. 3-O-sulfo (3-O-S) modification of HS has been linked to AD through its interaction with tau, and enhanced levels of 3-O-sulfated HS and 3-O-sulfotransferases in the AD brain. In this study, we characterized ApoE/HS interactions in wildtype ApoE3, AD-linked ApoE4, and AD-protective ApoE2 and ApoE3-Christchurch. Glycan microarray and SPR assays revealed that all ApoE isoforms recognized 3-O-S. NMR titration localized ApoE/3-O-S binding to the vicinity of the canonical HS binding motif. In cells, the knockout of HS3ST1-a major 3-O sulfotransferase-reduced cell surface binding and uptake of ApoE. 3-O-S is thus recognized by both tau and ApoE, suggesting that the interplay between 3-O-sulfated HS, tau and ApoE isoforms may modulate AD risk.     

ChemInform Abstract: Gas Phase Uranyl Activation: Formation of a Uranium Nitrosyl Complex from Uranyl Azide.

The fragmentation chemistry of UO₂(N₃)Cl₂^‐ (obtained by electrospray ionization of MeOH solutions containing UO₂Cl₂ and NaN₃) in the gas phase is investigated using quadrupole ion trap mass spectrometry.