US 11,946,041 B2
Modification of polypeptides
Liuhong Chen, Cambridge (GB); Michael Skynner, Cambridge (GB); Amy Brown, Cambridge (GB); James Cooke, Cambridge (GB); and Rachid Lani, Cambridge (GB)
Assigned to BicycleRD Limited, Cambridge (GB)
Appl. No. 16/607,378
Filed by BicycleRD Limited, Cambridge (GB)
PCT Filed Apr. 24, 2018, PCT No. PCT/EP2018/060498
§ 371(c)(1), (2) Date Oct. 23, 2019,
PCT Pub. No. WO2018/197509, PCT Pub. Date Nov. 1, 2018.
Claims priority of application No. 1706477 (GB), filed on Apr. 24, 2017.
Prior Publication US 2020/0407709 A1, Dec. 31, 2020
Int. Cl. C12N 15/10 (2006.01)
CPC C12N 15/1037 (2013.01) 17 Claims
 
1. A method for screening a library of peptide ligands that bind to a cell surface, said library comprising a plurality of polypeptides covalently linked to a molecular scaffold at three or more amino acid residues, comprising the steps of:
(a) displaying said library of peptide ligands in a genetic display system, wherein the polypeptide comprises three or more reactive groups, each of which forms a covalent linkage to the molecular scaffold, and at least two loops, each of which comprises a sequence of amino acids subtended between two of said reactive groups;
(b) exposing the peptide ligands to one or more target molecules which are present in a lipid bilayer membrane system during the screening; and
(c) screening the peptide ligands for binding against the target, and selecting the ligands which bind to the target,
wherein the peptide ligands bind in a pocket on the target on the surface or close to the surface.