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A current perspective on applications of macrocyclic‐peptide‐based high‐affinity ligands
Author(s) -
Leenheer Daniël,
ten Dijke Peter,
Hipolito Christopher John
Publication year - 2016
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22900
Subject(s) - chemistry , monoclonal antibody , combinatorial chemistry , peptide , computational biology , peptide library , antibody , binding selectivity , biochemistry , nanotechnology , biophysics , peptide sequence , immunology , gene , biology , materials science
Monoclonal antibodies can bind with high affinity and high selectivity to their targets. As a tool in therapeutics or diagnostics, however, their large size (∼150 kDa) reduces penetration into tissue and prevents passive cellular uptake. To overcome these and other problems, minimized protein scaffolds have been chosen or engineered, with care taken to not compromise binding affinity or specificity. An alternate approach is to begin with a minimal non‐antibody scaffold and select functional ligands from a de novo library. We will discuss the structure, production, applications, strengths, and weaknesses of several classes of antibody‐derived ligands, that is, antibodies, intrabodies, and nanobodies, and nonantibody‐derived ligands, that is, monobodies, affibodies, and macrocyclic peptides. In particular, this review is focussed on macrocyclic peptides produced by the Ra ndom non‐standard P eptides I ntegrated D iscovery (RaPID) system that are small in size (typically ∼2 kDa), but are able to perform tasks typically handled by larger proteinaceous ligands.