Peptide libraries having enhanced subsequence diversity and methods for use thereof

Patent metadata

Field	Value
Publication number	US-12595591-B2
Application number	US-202017622479-A
Country	US
Kind code	B2
Filing date	Jun 26, 2020
Priority date	Jun 27, 2019
Publication date	Apr 7, 2026
Grant date	Apr 7, 2026

Abstract

The present technology provides an approach to designing libraries of peptide sequences for discovery and testing of significantly more motifs than would be otherwise available in a given fixed library format. The technology includes a plurality of x-mers embedded in N-mer peptides sequences, where N and x are integers and where N is greater than x. This approach provides for the representation of multiple unique x-mer peptides in a single N-mer peptide feature.

First claim

What is claimed is:

1 . A method for identifying a peptide binder, the method comprising:
contacting a first sample with an engineered peptide library; selecting at least one of the plurality of peptides from the first subset of peptides; detecting a first signal output characteristic of an interaction of the sample with the engineered peptide library; and selecting the at least one peptide, which binds to the sample, based on the first signal output; wherein the engineered peptide library comprises:
a plurality of peptide features, each of the peptide features including at least one peptide, the at least one peptide comprising a composite region having a defined sequence of amino acids of length N, the composite region representing k different elements, each of the different elements having defined sequence of amino acids of length x; wherein
x, N and k are integers,
x is less than N,
k is at least 2 and is defined by the equation, k=N−x+1,
a total number of different elements represented by the engineered peptide library is K Eng ,
the number of peptide features included in the engineered peptide library is F, and
K Eng is at least 0.8*k*F.

2 . The method of claim 1 , wherein the first signal output is a fluorescence intensity obtained through fluorophore excitation-emission, the fluorescence intensity reflecting at least one of:
i) an abundance of a component of one of the first sample and a second sample associated with the first plurality of peptides, and ii) a binding affinity of the component of one of the first sample and a second sample to the first plurality of peptides.

3 . The method of claim 1 , wherein the first sample comprises a receptor, antibody, enzyme, peptide, or an oligonucleotide.

4 . The method of claim 1 , wherein K Eng is at least 0.9*k*F.

5 . The method of claim 1 , wherein K Eng is at least 0.95*k*F.

6 . The method of claim 1 , wherein K Eng is at least 0.99*k*F.

7 . The method of claim 1 , wherein K Eng is at least 10*F.

8 . The method of claim 1 , wherein K Eng is at least 20*F.

9 . The method of claim 1 , wherein each of the elements in a selected one of the composite regions overlaps with each adjacent element in the composite region by at least 1 amino acid.

10 . The method of claim 1 , wherein the plurality of peptides represents at least 90% of a human proteome.

11 . The method of claim 1 , wherein N is at least 7 amino acids.

12 . The method of claim 1 , wherein N is at least 10 amino acids.

13 . The method of claim 1 , wherein N is at least 15 amino acids.

14 . The method of claim 1 , wherein x is at least 5 or at least 6.

Assignees

• Roche Sequencing Solutions Inc

Inventors

• Goodrich Lauren
• Lyamichev Victor
• Patel Jigar
• Pinapati Richard
• Sullivan Eric
• Richmond Todd

Classifications

• G16B35/10

  Design of libraries · CPC title

• G16B20/30

  Detection of binding sites or motifs · CPC title

• C40B40/10

  Libraries containing peptides or polypeptides, or derivatives thereof · CPC title

• C40B30/04 Primary

  by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding · CPC title

• C12N15/1034 Primary

  Isolating an individual clone by screening libraries · CPC title