The present invention concerns compounds that are capable of covalently entrapping adenylating enzymes. The present invention is essentially based on the discovery that analogues of adenylating enzyme (AE) substrates, wherein a methylene group has been incorporated at the carbon atom in the α-position relative to the carboxylate group involved in the adenylation, are capable of undergoing the adenylation reaction, thereby creating an activated methylene group in situ. The resulting ‘armed’ acyladenylate can interact with the enzyme resulting in covalent entrapment. Interestingly, the acyladenylate can alternatively be transferred to the next step in the enzyme cascade, following which the activated methylene group can interact with the next (active site cysteine containing) enzyme in the enzymatic cascade. The AE substrate analogues, based on their capability of ‘entrapping’ the respective enzymes, will have utility as activity based probes in biological research and also as diagnostic and/or therapeutic agents.

Provided herein are nicotinamide adenine dinucleotide analogues, compositions comprising such compounds, and methods of using such analogues and compositions.

The present disclosure provides NAD analogs of the formula: ##STR00001## wherein R.sub.1, n, and X.sub.1 are defined herein, useful for the identification of PARP target proteins and the amino acid sequence wherein the ribose group is attached to the target protein. Also, provided herein are methods of identifying target protein and amino acid sequences. Additionally, the present disclosure provides methods of identifying DNA sequences associated with specific chromatin proteins.

The present disclosure relates to methods for high throughput analysis of analytes such as polypeptides in a cyclic manner (e.g., using NGPA or NGPS described herein) that allow adjustment of the dynamic range and sensitivity of analyte detection, for instance, based on the abundances of different polypeptides present in a sample to be analyzed. The approaches proposed herein can be used to adjust the dynamic range of abundant analytes (e.g., polypeptides present in high concentrations) in biological samples, such as plasma samples, and to increase proteome coverage achieved by high throughput protein analysis methods, for instance, by improving the sensitivity of detecting less abundant analytes.