Triad National Security, LLC

University of California

Charlie E Strauss

Ramesh K Jha

Jurgen G Schmidt

Robert F Williams

Robert David Gilbertson

Taraka Dale

Tsutomu Shimada

Carl W Wilson

Thomas J Zaugg

George E Busch

Andrew M Bradbury

Dennis K Remelius

Paul William Peterson

David C Thompson

Biosensors including a nucleic acid encoding a PcaU protein, a PobR protein, a CatM protein, a PcaR protein, or a TphR protein are provided. In some examples, the biosensors include a promoter regulated by the sensed molecule operably linked to a reporter gene. The biosensors may be included in a vector or in cells including one or more of the biosensors or vectors. Modified chorismate pyruvate lyase (UbiC) and modified paraoxonase (PON1) proteins including one or more amino acid substitutions are provided. Finally, methods of selecting biocatalysts with increased activity including transforming a library of cells expressing a biosensor with one or more nucleic acids encoding one or more mutations in a gene involved in a biosynthesis pathway, determining activity of the reporter protein; and selecting a cell with increased reporter protein activity as expressing a biocatalyst with increased activity are provided.

Modified biosensors and biocatalysts and methods of use

The present disclosure provides improved methods for controlled cyclization of peptoid dimers to form N,N'-2,5-diketopiperazines (N,N&#x2032;-2,5-DKPs) with significant selectivity. In at least some examples, selectivity is based on a serendipitous conglomeration of slow exchange of amide rotamers, steric repulsion from the degree of &#x3b1;-substitution, and the geometric bulk of an amine nucleophile. By varying reaction conditions, the selectivity of the reaction and formation of a particular N,N&#x2032;-2,5-DKP can be switched. The cyclization works in the presence of a variety of protection groups and diverse functionalities. The teachings herein provide techniques for synthesizing N,N&#x2032;-2,5-DKPs that can be readily docked with drug candidates for shuttling across the blood brain barrier. This method provides a facile way to produce substituted DKPs containing groups ready for post-modification to include docking drug candidates.

Controlled cyclization of peptoids to form chiral diketopiperazines

Modified Fc-binding domain polypeptides or polypeptides including one or more modified Fc-binding domains are provided. In some examples, a modified Fc-binding domain includes or consists of the amino acid sequence of any one of SEQ ID NOs: 4, 6, or 8. Nucleic acids encoding the modified Fc-binding domains or polypeptides including one or more of the modified Fc-binding domains are also provided. In some embodiments, the nucleic acids are included in a vector and may be operably linked to a promoter. Methods for purifying a polypeptide including one or more Fc regions are also provided. Kits and reagents including the modified Fc-binding domain polypeptides or polypeptides including one or more modified Fc-binding domains are provided. In some examples, the modified Fc-binding domain polypeptides or polypeptides including one or more modified Fc-binding domains are linked to a solid support.

Designed proteins for pH switchable antibody purification

The present invention describes the use of a pair of acoustooptic devices in a laser or other optical resonator to produce a wavelength-dependent deflection of the light without incurring a net frequency shift. This permits rapid electronic tuning of the resonator wavelength, as well as rapid electronic variation of cavity loss, out-coupling fraction, and round-trip phase shift. The dispersive quality of acoustooptic devices in transmission is utilized as a reflection grating substitute. Two mirrors, one an output coupler, a gain medium and two acoustooptic devices arranged for maximum efficiency such that the incident and diffracted beams are approximately at the Bragg angle for each acoustooptic device permit the laser wavelength to be determined by the acoustic frequency.

Rapid acoustooptic tuner and phase-shifter

Apparatus and method for heterodyne-generated, two-dimensional detector array using a single detector. Synthetic-array heterodyne detection, permits a single-element optical detector to behave as though it were divided into an array of separate heterodyne detector elements. A fifteen-element synthetic array has successfully been experimentally realized on a single-element detector, permitting all of the array elements to be read out continuously and in parallel from one electrical connection. A CO.sub.2 laser and a single-element HgCdTe photodiode are employed. A different heterodyne local oscillator frequency is incident upon the spatially resolvable regions of the detector surface. Thus, different regions are mapped to different heterodyne beat frequencies. One can determine where the photons were incident on the detector surface even though a single electrical connection to the detector is used. This also prevents the destructive interference that occurs when multiple speckles are imaged (similar to spatial diversity), In coherent LIDAR this permits a larger field of view. An acoustooptic modulator generates the local oscillator frequencies and can achieve adequate spatial separation of optical frequencies of the order of a megahertz apart.

Apparatus and method for heterodyne-generated two-dimensional detector

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Los Alamos, NM, United States of America

Charlie E Strauss