University of Texas System

Jagannath Swaminathan

Andrew D Ellington

Eric V Anslyn

Edward M Marcotte

Alexander Boulgakov

Erik Hernandez

Helen Seifert

Amber Johnson

Edward Marcotte

James L Bachman

Raghav Shroff

Sanchita Bhadra

Brendan Floyd

Jon Laurent

Erhu Xiong

Methods of identifying a sequence of a polypeptide within a heterogenous mixture of polypeptides, the polypeptide being immobilized to a support and having at least one labeled amino acid residue. Methods involve detecting at least one signal or signal change from the immobilized polypeptide and subjecting the polypeptide to conditions sufficient to remove at least one amino acid residue from the polypeptide.

Single molecule peptide sequencing

The present disclosure provides methods for molecular neighborhood detection of molecules, such as by iterative proximity ligation or split-and-pool methods for obtaining positional information.

Molecular neighborhood detection by oligonucleotides

Identifying proteins and peptides, and more specifically large-scale sequencing of single peptides in a mixture of diverse peptides at the single molecule level is an unmet challenge in the field of protein sequencing. Herein are methods for identifying amino acids in peptides, including peptides with unnatural amino acids. In one embodiment, the N-terminal amino acid is labeled with a first label and an internal amino acid is labeled with a second label. In some embodiments, the labels are fluorescent labels. In other embodiments, the internal amino acid is Lysine. In other embodiments, amino acids in peptides are identified based on the fluorescent signature for each peptide at the single molecule level.

The disclosure concerns methods for identifying amino acids in peptides, including peptides including unnatural amino acids. Various aspects of the present disclosure provide compositions and methods for amino acid-type specific labeling, as well as methods for detecting the labels. Further disclosed herein are strategies for highly multiplexed, high-throughput peptide analysis.

The present invention relates to methods for identifying amino acids in peptides. In one embodiment, the present invention contemplates labeling the N-terminal amino acid with a first label and labeling an internal amino acid with a second label. In some embodiments, the labels are fluorescent labels. In other embodiments, the internal amino acid is lysine. In other embodiments, amino acids in peptides are identified based on the fluorescent signature for each peptide at the single molecule level.

Identifying peptides at the single molecule level

Identifying proteins and peptides, and more specifically large-scale sequencing of single peptides in a mixture of diverse peptides at the single molecule level is an unmet challenge in the field of protein sequencing. Herein are methods for identifying amino acids in peptides, including peptides with one or more unnatural amino acids. In one embodiment, the N-terminal amino acid is labeled with a first label and an internal amino acid is labeled with a second label. In some embodiments, the labels are fluorescent labels. In other embodiments, the internal amino acid is Lysine. In other embodiments, amino acids in peptides are identified based on the fluorescent signature for each peptide at the single molecule level.

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Austin, TX, United States of America

Jagannath Swaminathan