SOLUTION-PHASE AFFINITY SELECTION OF INHIBITORS FROM COMBINATORIAL PEPTIDE LIBRARIES

Title:

SOLUTION-PHASE AFFINITY SELECTION OF INHIBITORS FROM COMBINATORIAL PEPTIDE LIBRARIES

Document Type and Number:

WIPO Patent Application WO/2019/133179

Kind Code:

A3

Abstract:

The present invention provides novel peptides (e.g., peptides, macrocyclic peptides, mini-proteins) that modulate protein-protein interactions or salts thereof, and methods of making and using the inventive peptides. In some embodiments, the peptides are high affinity inhibitors (e.g., KD of at most 100 nM, at most 10 nM, at most 1 nM) of a protein-protein interaction. In certain embodiments, these peptides interfere with p53-MDM2 binding interactions (e.g., by binding to MDM2 (GenBank® Gene ID: 4193)). In some embodiments, the peptides interfere with the dimerization of the C-terminal domain of the human immunodeficiency virus (HIV) capsid protein (C-CA), comprising residues 146-231 of the HIV capsid protein (e.g., by binding to the C-terminal domain of the HIV capsid protein (C-CA), thereby inhibiting the dimeric interface of HIV capsid protein, thereby inhibiting viral assembly). These inventive peptides were rapidly generated and identified using novel methods described herein comprising combinatorial peptide synthesis and/or solution affinity selection.

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Inventors:

PENTELUTE BRADLEY (US)
TOUTI FAYCAL (US)

Application Number:

PCT/US2018/063342

Publication Date:

December 26, 2019

Filing Date:

November 30, 2018

Export Citation:

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Assignee:

MASSACHUSETTS INST TECHNOLOGY (US)

International Classes:

C07K7/04; C07K7/02; C07K11/02; C07K14/155; C07K14/475; C40B40/10

Domestic Patent References:

WO2008106507A2	2008-09-04
WO2017015630A2	2017-01-26

Foreign References:

US20140308267A1	2014-10-16
US20100130430A1	2010-05-27
US20140113871A1	2014-04-24
US20130210743A1	2013-08-15
US20120328692A1	2012-12-27

Attorney, Agent or Firm:

HAMZIK, Philip, J. (US)

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