Massachusetts Institute of Technology

Andrei Tokmakoff

Matthew F DeCamp

Lauren DeFlores

John M Essigmann

Bogdan I Fedeles

Chunte Peng

Carlos R Baiz

Vipender Singh

Kevin C Jones

The present disclosure provides nucleoside analogs of Formula (I) or (II). The nucleoside analogs are expected to show multiple tautomerism and may increase the mutation of an RNA and/or DNA (be mutagenic) of a virus or cancer cell. The multiple tautomerism and mutagenesis of the nucleoside analogs may be adjusted by substituting the nucleoside analogs with one or more electron-donating groups and/or electron-withdrawing groups to increase or decrease the pK(e.g., to a pKbetween 5.5 or 8.5). The present disclosure also provides pharmaceutical compositions and kits including the nucleoside analogs and methods of treating a viral infection (e.g., influenza, HIV infection, or hepatitis) or cancer using the nucleoside analogs, pharmaceutical compositions, or kits.

Mutagenic nucleoside analogs and uses thereof

The present invention relates to a system and methods for acquiring two-dimensional Fourier transform (2D FT) spectra. Overlap of a collinear pulse pair and probe induce a molecular response which is collected by spectral dispersion of the signal modulated probe beam. Simultaneous collection of the molecular response, pulse timing and characteristics permit real time phasing and rapid acquisition of spectra. Full spectra are acquired as a function of pulse pair timings and numerically transformed to achieve the full frequency-frequency spectrum. This method demonstrates the ability to acquire information on molecular dynamics, couplings and structure in a simple apparatus. Multi-dimensional methods can be used for diagnostic and analytical measurements in the biological, biomedical, and chemical fields.

Two-dimensional fourier transform spectrometer

The present invention relates to systems and methods for the determination of the secondary structure composition of proteins using coherent two-dimensional infrared (2DIR) spectroscopy of backbone amide I vibrations (1580-1720 cm). Fractions of &#x3b1;-helix, &#x3b2;-sheet, and unassigned regions in globular proteins were determined by singular value decomposition using basis spectra from sixteen commercially-available proteins with known crystal structures. Preferred methods included removing each protein from the set and comparing the predicted composition against the crystal structure. The root-mean-squared (RMS) errors of the predicted secondary structure compositions were found to be 7.9% for &#x3b1;-helix, 5.5% for &#x3b2;-sheet, and 7.6% for unassigned regions. The structure analysis can also be performed using one-dimensional absorption spectra and the RMS errors are compared with those obtained from 2DIR.

Vibrational spectroscopy for quantitative measurement of analytes

Preferred embodiments of the invention provide for methods and systems of 2D spectroscopy using ultrafast, first light and second light beams and a CCD array detector. A cylindrically-focused second light beam interrogates a target that is optically interactive with a frequency-dispersed excitation (first light) pulse, whereupon the second light beam is frequency-dispersed at right angle orientation to its line of focus, so that the horizontal dimension encodes the spatial location of the second light pulse and the first light frequency, while the vertical dimension encodes the second light frequency. Differential spectra of the first and second light pulses result in a 2D frequency-frequency surface equivalent to double-resonance spectroscopy. Because the first light frequency is spatially encoded in the sample, an entire surface can be acquired in a single interaction of the first and second light pulses.

Method and apparatus for two-dimensional spectroscopy

The invention relates to methods and apparatus for modifying the frequency characteristics of a spatially-dispersed mid-IR spectra for spectroscopy. In a preferred embodiment, sum frequency generation between a frequency-dispersed IR beam and an ultrafast optical pulse generates a spatially-extended optical signal that is collected with a CCD detector.

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Lexington, MA, United States of America

Andrei Tokmakoff