The invention provides a compound of formula I:

##STR00001##

wherein R.sub.1-R.sub.6 and X have any of the values described herein, as well as pharmaceutical compositions comprising such compounds and therapeutic methods comprising the administration of such compounds.

The invention provides a compound of formula I:

##STR00001##

wherein R.sub.1-R.sub.6 and X have any of the values described herein, as well as pharmaceutical compositions comprising such compounds and therapeutic methods comprising the administration of such compounds.

The current disclosure provides methods for detecting and quantitating the 6-O-methylguanine-DNA methyltransferase protein (MGMT) directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed with formaldehyde containing agents/fixatives and may include formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and/or paraffin embedded. A protein sample is prepared from the biological sample and the MGMT protein is quantitated in the sample using SRM/MRM mass spectrometry by quantitating one or more fragment peptides.

The present invention provides novel peptidomimetic macrocycles and methods for their preparation and use, as well as amino acid analogs and macrocycle-forming linkers, and kits useful in their production.

The present invention provides novel peptidomimetic macrocycles and methods for their preparation and use, as well as amino acid analogs and macrocycle-forming linkers, and kits useful in their production.

Some aspects of the disclosure include methods for comparing the higher order structures (HOS) of proteins using covalent labeling agents which allow for the direct comparison of changes in the HOS of protein therapeutics using mass spectrometry. The inventive methods can be used to access the effect of changing the process of producing and/or storing complex biologic compounds as well as determining if the HOS of a protein therapeutic has spontaneously changed during storage. Still other uses include comparing branded biologic therapeutic compounds to biosimilar compounds, and measuring changes in the aggregation states of proteins.

The disclosure provides cationic peptidopolysaccharides of Formula I: which has a bacterial peptidoglycan-mimetic structure, and shows outstanding broad spectrum activities against clinically significant bacteria and fungi. The structural affinity of these compounds with microbial cell wall constituents promotes its passage to the cytoplasmic membrane resulting in excellent antimicrobial activity and record high selectivity. The disclosure also describes methods of making and using cationic peptidopolysaccharides of Formula I.

The disclosure provides cationic peptidopolysaccharides of Formula I: which has a bacterial peptidoglycan-mimetic structure, and shows outstanding broad spectrum activities against clinically significant bacteria and fungi. The structural affinity of these compounds with microbial cell wall constituents promotes its passage to the cytoplasmic membrane resulting in excellent antimicrobial activity and record high selectivity. The disclosure also describes methods of making and using cationic peptidopolysaccharides of Formula I.

The invention relates to method for quantification of the absolute amount of allergen in an allergen sample comprising: a) providing a known amount of one or more allergen calibration standard peptide(s) having a sequence of amino acids which is identical with, and optionally unique for, a sequence to be found in the allergen to be quantified and optionally labelling said allergen calibration standard peptide(s), b) degrading the allergen sample to obtain a mixture of peptides, and optionally labelling said peptides with one or more labelling agent(s),
wherein at least the peptides in the degraded allergen sample or the calibration standard peptides are labelled, and if both the peptides in the degraded allergen sample and the allergen calibration standard peptide(s) are labelled, the labelling agent(s) used for labelling the allergen calibration standard peptide(s) are different from the labelling agent(s) used for labelling the peptides of the degraded allergen sample, c) quantifying the absolute amount of allergen by correlating the amount of the allergen calibration standard peptide(s) with the amount of the corresponding peptide(s) of the degraded allergen sample by mass analysis.

The inventive subject matter relates to the methods for the induction of immunity and prevention of diarrhea resulting from Escherichia coli. The inventive subject matter also relates to the use Escherichia coli adhesins as immunogens and to the construction of conformationally stability and protease resistant Escherichia coli adhesin constructs useful for inducing immunity to Escherichia coli pathogenic bacteria. The methods provide for the induction of B-cell mediated immunity and for the induction of antibody capable of inhibiting the adherence and colonization of Escherichia coli, including enterotoxigenic Escherichia coli, to human cells.