Back to results
US 10,466,249 B2Granted
Methods and reagents for analyzing protein-protein interfaces
AssigneeRevolution Medicines, Inc.
InventorsGregory L. Verdine, M. James Nichols, Sharon A. Townson, Uddhav Kumar Shigdel, Seung-Joo Lee, Dylan T. Stiles, Neville J. Anthony
Life of this patent
Estimating the term…
Abstract
The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.
Claims2
A compound having the structure:
- A-L-B
- wherein A has the structure of Formula Ila:
- wherein Z1 and Z2 are each, independently, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl;
- and Z2 includes a point of attachment to the L;
- X2 is absent, CH2, O, S, SO, SO2, or NR4;
- each R4 is, independently, hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted aryl, C3-C7carbocyclyl, optionally substituted C6-C10 aryl C1-C6 alkyl, and optionally substituted C3-C7 carbocyclyl C1-C6 alkyl;
- L is a linker having the structure:
- A1-(B1)f—(C1)g—(B2)h-(D)-(B3)i—(C2)j—(B4)k-A2
- wherein A1 is a bond between the linker and A;
- A2 is a bond between B and the linker;
- B1, B2, B3, and B4 each, independently, is selected from optionally substituted C1-C2 alkyl, optionally substituted C1-C3 heteroalkyl, O, S, and NRN;
- RN is hydrogen, optionally substituted C1-C4 alkyl, optionally substituted C2-4 alkenyl, optionally substituted C2-4 alkynyl, optionally substituted C2-6 heterocyclyl, optionally substituted C6-12 aryl, or optionally substituted C1-7 heteroalkyl;
- C1 and C2 are each, independently, selected from carbonyl, thiocarbonyl, sulphonyl, or phosphoryl;
- f, g, h, i, j, and k are each, independently, 0 or 1;
- and D is optionally substituted C1-10 alkyl, optionally substituted C2-10 alkenyl, optionally substituted C2-10 alkynyl, optionally substituted C2-6 heterocyclyl, optionally substituted C6-12 aryl, optionally substituted C2-C10 polyethylene glycol, or optionally substituted C1-10 heteroalkyl, or a chemical bond linking A1-(B1)f13 (C1)g—(B2)h— to —(B3)i—(C2)j—(B4)k-A2;
- and
- B comprises a cross-linking group, wherein the cross-linking group is a maleimide, vinyl sulfone, isocyanate, isothiocyanate, sulfonyl chloride, acid anhydride, acylazide, imidoester, haloheteroaryl, diazo, carbodiimide, hydrazide, or alkoxyamine,
- or a salt thereof.
15 more elements
Dependencies are inferred from the claim text.