A search algorithm for fixed-composition protein design

We present a computational protein design algorithm for finding low-energy sequences of fixed amino acid composition. The search algorithms used in protein design typically do not restrict amino acid composition. However, the random energy model of Shakhnovich suggests that the use of fixed-composition sequences may circumvent defects in the modeling of the denatured state. Our algorithm, FC_FASTER, links fixed-composition versions of Monte Carlo and the FASTER algorithm. As proof of principle, FC_FASTER was tested on an experimentally validated, full-sequence design of the beta1 domain of protein G. For the wild-type composition, FC_FASTER found a lower energy sequence than the experimentally validated sequence. Also, for a different composition, FC_FASTER found the hypothetical lowest-energy sequence in 14 out of 32 trials.     

The synthesis of bis(oligophenyleneethynylenes): novel potential nonlinear optical materials

Various functionalised phenyleneethynylene dimers 10 and trimers 12 were synthesised by palladium-catalyzed Sonogashira methodology. These dimers and trimers were coupled to 1,8-diido-10-methoxyanthracene to generate bis(oligophenyleneethynylenes) 17 and 18. Preliminary results towards the construction of both phenyleneethynylene and phenylenevinylene hybrid motifs are presented.     

On extensions of the Baer-Suzuki Theorem

We find a necessary and sufficient condition for an element of prime order in a finite group to be in a normalp-subgroup. This generalizes the Baer-Suzuki Theorem. Our proof depends on a result about elements of prime order contained in a unique maximal subgroup containing a result of Wielandt. We discuss various consequences, linear and algebraic group versions of the result. For John Thompson Partially supported by NSF grant DMS-91011407. Partially supported by NSF grant DMS-9208667.     

Toward the development of a general chiral auxiliary. A total synthesis of (+)-tetronolide via a tandem ketene-trapping [4 + 2] cycloaddition strategy

A highly convergent, enantioselective total synthesis of the aglycone of the tetrocarcins, (+)-tetronolide, is described. The synthesis highlights the use of several new methods, including camphor auxiliary-directed asymmetric alkylation and the enantioselective preparation of acyclic mixed acetals bearing chirality at the acetal center, and the highly efficient connection of the two major precursors via a ketene-trapping/intramolecular [4 + 2] cycloaddition strategy.     

Characteristics of an optically pumped COF2 laser

An optically pumped COF₂ laser^1,2 has been used for experiments with NbN Josephson junctions at NPL³. Its characteristics are described in this paper, with particular reference to results of output power stability and output power level⁴.     

Quantum mechanics in a discrete model of classical physics

The role of probability theory in classical physics is examined. It is found that the probabilities for the outcomes of typical experiments depend strongly on the assumed behavior of given classical models at infinity. A discrete classical model is introduced and it is shown that the resulting probabilities are similar to those in the usual theory of quantum mechanics.     

Rational Design of Mono- and Bi-Nuclear Cyclometalated Ir(III) Complexes Containing Di-Pyridylamine Motifs: Synthesis,Structure, and Luminescent Properties

Heteroleptic cyclometalated iridium (III) complexes (1–3) containing di-pyridylamine motifs were prepared in a stepwise fashion. The presence of the di-pyridylamine ligands tunes their electronic and optical properties, generating blue phosphorescent emitters at room temperature. Herein we describe the synthesis of the mononuclear iridium complexes [Ir(ppy)₂(DPA)][OTf] (1), (ppy = phenylpyridine; DPA = Dipyridylamine) and [Ir(ppy)₂(DPA-PhI)][OTf] (2), (DPA-PhI = Dipyridylamino-phenyliodide). Moreover, the dinuclear iridium complex [Ir(ppy)₂(L)Ir(ppy)₂][OTf]₂ (3) containing a rigid angular ligand “L = 3,5-bis[4-(2,2′-dipyridylamino)phenylacetylenyl]toluene” and displaying two di-pyridylamino groups was also prepared. For comparison purposes, the related dinuclear rhodium complex [Rh (ppy)₂(L)Rh(ppy)₂][OTf]₂ (4) was also synthesized. The x-ray molecular structure of complex 2 was reported and confirmed the formation of the target molecule. The rhodium complex 4 was found to be emissive only at low temperature; in contrast, all iridium complexes 1–3 were found to be phosphorescent in solution at 77 K and room temperature, displaying blue emissions in the range of 478–481 nm.     

Synthesis of a dicarba analogue of human β-defensin-1 using a combined ring closing metathesis--native chemical ligation strategy

We herein describe the first synthesis of the native antimicrobial protein HBD-1 making use of an orthogonal thiol protection strategy and a novel dicarba analogue thereof. The robust hydrocarbon linkage was installed by replacement of one disulfide bond using on-resin ring closing metathesis. The unprecedented 59-membered C-terminal cysteine macrocyclic fragment thus formed then engages in native chemical ligation allowing convergent access to this unique synthetic protein analogue.