Crystal structure of a human MUC16 SEA domain reveals insight into the nature of the CA125 tumor marker.

MUC16 is a membrane bound glycoprotein involved in the progression and metastasis of pancreatic and ovarian cancer. The protein is shed into the serum and the resulting cancer antigen 125 (CA125) can be detected by immunoassays. The CA125 epitope is used for monitoring ovarian cancer treatment progression, and has emerged as a potential target for antibody mediated immunotherapy.

ImmunoPET of Ovarian and Pancreatic Cancer with AR9.6, a Novel MUC16-Targeted Therapeutic Antibody.

Purpose: Advances in our understanding of the contribution of aberrant glycosylation to the pro-oncogenic signaling and metastasis of tumor cells have reinvigorated the development of mucin-targeted therapies. Here, we validate the tumor-targeting ability of a novel monoclonal antibody (mAb), AR9.6, that binds MUC16 and abrogates downstream oncogenic signaling to confer a therapeutic response.

Structure of a VH isolated from a naïve phage display library.

Objective: To determine the X-ray structure and biophysical properties of a Camelid VH isolated from a naïve phage display library.

Results: Single domain antibodies (VH) derived from the unique immune system of the Camelidae family have gained traction as useful tools for biotechnology as well as a source of potentially novel therapeutics. Here we report the structure and biophysical characterization of a VH originally isolated from a naïve camelid phage display library.

Reduction of Non-Specific Protein Adsorption Using Poly(ethylene) Glycol (PEG) Modified Polyacrylate Hydrogels In Immunoassays for Staphylococcal Enterotoxin B Detection.

Three PEG molecules (PEG-methacrylate, -diacrylate and -dimethacrylate) were incorporated into galactose-based polyacrylate hydrogels and their relative abilities to reduce non-specific protein adsorption in immunoassays were determined. Highly crosslinked hydrogels containing amine-terminated functionalities were formed and used to covalently attach antibodies specific for staphylococcal enterotoxin B (SEB). Patterned arrays of immobilized antibodies in the PEG-modified hydrogels were created with a PDMS template containing micro-channels for use in sandwich immunoassays to detect SEB.

Optical solid-state detection of organophosphates using organophosphorus hydrolase.

We have developed a sensor surface for optical detection of organophosphates based on reversible inhibition of organophosphorus hydrolase (OPH) by copper complexed meso-tri(4-sulfonato phenyl) mono(4-carboxy phenyl) porphyrin (CuC1TPP). OPH immobilized onto glass microscope slides retains catalytic activity for more than 232 days. CuC1TPP is a reversible, competitive inhibitor of OPH, binding at the active site of the immobilized enzyme.

Extended lifetime of reagentless detector for multiple inhibitors of acetylcholinesterase.

Competitive inhibitors of acetylcholinesterase (AChE) are detected using an evanescent wave technique to monitor changes in the absorbance spectrum of an AChE-monosulfonate tetraphenyl porphyrin (TPPS(1)) complex immobilized on the surface of a glass slide. In this technique, porphyrin is displaced from the AChE active site by the inhibitor. The loss in absorbance intensity of the characteristic absorbance peak for the AChE-TPPS(1) complex at 446 nm is linearly dependent on the log of the inhibitor concentration.

Novel optical solid-state glucose sensor using immobilized glucose oxidase.

Meso-tetra(4-carboxyphenyl)porphine (CTPP(4)) binds reversibly to immobilized glucose oxidase (GOD), resulting in an absorbance peak for the CTPP(4)-GOD complex at 427nm. The absorbance intensity of the 427nm peak is reduced upon exposure to glucose, which causes the dissociation of CTPP(4) from GOD. The change in absorbance at 427nm shows linear dependence on glucose concentration from 20 to 200mg/dL (1.

Interaction of monosulfonate tetraphenyl porphyrin, a competitive inhibitor, with acetylcholinesterase.

Monosulfonate tetraphenyl porphyrin (TPPS(1)) forms a 1:1 complex with electric eel acetylcholinesterase (AChE) inducing a loss in TPPS(1) absorbance at 402 nm and the appearance of a new absorbance centered at 442 nm. In the presence of AChE, the fluorescence of TPPS(1) at 652 nm is slightly narrowed, with the maximal 652 nm fluorescence shifted from 407 to 412 nm excitation wavelength. The fluorescence peak of TPPS(1) at 712 nm shifts to 716 nm in the presence of AChE.

Reagent-less detection of a competitive inhibitor of immobilized acetylcholinesterase.

The interaction of monosulfonate tetraphenyl porphine (TPPS(1)) with immobilized acetylcholinesterase (AChE) yields a characteristic absorbance peak at 446 nm. Addition of acetylcholine iodide or the competitive inhibitor tetracaine to the immobilized TPPS(1)-AChE complex results in a decrease in absorbance intensity at 446 nm due to displacement of the porphyrin from the active site. The loss in intensity at 446 nm is linearly dependent on tetracaine concentration at levels below 100 ppb.