University of California

Yale University

Christina Woo

Carolyn Ruth Bertozzi

Peter M Glazer

Seth Herzon

Methods for producing isotopically-labelled peptides are provided. Aspects of the method include: contacting a sample including a metabolically tagged protein with a cleavable probe to produce a probe-protein conjugate; separating the probe-protein conjugate from the sample; digesting the probe-protein conjugate to produce a probe-peptide conjugate; and cleaving a cleavable linker to release an isotopically labelled peptide. The method may further include: identifying a predetermined isotopic pattern in a mass spectrum; determining an amino acid sequence of the isotopically labelled peptide; and identifying the site of protein glycosylation based on the determined amino acid sequence. Also provided are cleavable probes for practicing the subject methods, described by the Formula: A-L-(M-Z) where A is an affinity tag, L is a cleavable linker, M is an isotopic label and Z is a chemoselective tag capable of cross-linking a metabolically tagged protein. Compositions and kits for practicing the subject methods are also provided.

Cleavable probes for isotope targeted glycoproteomics and methods of using the same

The present invention is directed to novel anti-cancer compounds and methods of treating and/or inhibiting cancer in patients, including metastatic cancer, recurrent cancer and drug resistant cancers, including multiple drug resistant cancers. Compounds according to the present invention provide anti-cancer activity, at least in part, by virtue of their nucleotide intercalating activity through the use of analogs of (&#x2212;)lomaiviticin A, a potent anticancer agent which exhibits cytotoxicity through its principal mechanism of cleavage and to a lesser extent, its intercalation of cellular polynucleotides, especially DNA. In additional embodiments, compounds according to the present invention are also conjugated and/or linked to other bioactive agents, especially agents which selectively target cancer cells (cancer cell targeting moiety or CCTM) to target and increase the delivery of the anticancer agent to the cancer cell. These targeting agents include folate receptor-targeted moieties, other cancer binding moieties such as PMSA binding moieties as otherwise described herein and antibodies, including single chain variable fragment antibodies (scFv antibodies). Pharmaceutical compositions based upon these novel compounds are also disclosed pursuant to the present invention. Methods of treating, inhibiting and/or reducing the likelihood of cancer, including metastatic and recurrent cancer and drug resistant, including multiple drug resistant cancer in a patient are also disclosed.

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Berkeley, CA, United States of America

Christina Woo