title: A current perspective on applications of macrocyclic-peptide-based high-affinity ligands.
abstract: 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 Random non-standard Peptides Integrated Discovery (RaPID) system that are small in size (typically ∼2 kDa), but are able to perform tasks typically handled by larger proteinaceous ligands.
authors.affiliation: Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Daniël
authors.initials: D
authors.lastname: Leenheer
authors.affiliation: Leiden University Medical Center, Department of Molecular Cell Biology, Leiden, South Holland, The Netherlands.|Cancer Signaling, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Peter
authors.initials: P
authors.lastname: Ten Dijke
authors.affiliation: Cancer Signaling, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Christopher John
authors.initials: CJ
authors.lastname: Hipolito
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000915:Antibody Affinity; D006801:Humans; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D019151:Peptide Library; D010456:Peptides, Cyclic
keywords: RaPID system; antibodies; cocrystallization ligands; macrocyclic peptides