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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.

SUBMITTER: Leenheer D

PROVIDER: S-EPMC5132055 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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A current perspective on applications of macrocyclic-peptide-based high-affinity ligands.

Leenheer Daniël D Ten Dijke Peter P Hipolito Christopher John CJ

Biopolymers 20161101 6

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 liga ...[more]

PMID: 27352774

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Project description:Effective delivery of drug molecules to the target site is a challenging task. In the last decade, several innovations in the drug delivery system (DDS) have tremendously improved the therapeutic efficacy of drug molecules. Among various DDS, cell-penetrating peptides (CPPs) based DDS have gathered notable attention owing to their safety, efficacy, selectivity, specificity, and ease of synthesis. CPPs are emerging as an efficient and effective pharmaceutical nanocarriers-based platforms for successful management of various important human health disorders. Failure of several current chemotherapeutic strategies is attributed to low solubility, reduced bioavailability, and off-target delivery of several anti-cancer drugs. Similarly, development of therapeutics for vision-threatening disorders is challenged by the anatomical as well as physiological complexity of the eye. Such therapeutic challenges in cancer and ocular disease management can be overcome by developing cell-penetrating peptide (CPP) based peptide drug conjugates (PDCs). CPPs can be used to deliver various types of cargo molecules including nucleic acids, small molecules, and peptides/proteinaceous agents. In this review, we have briefly introduced CPPs and the linker strategies employed for the development of PDCs. Furthermore, recent studies employing CPP-based PDCs for cancer and ocular disease management have been discussed in detail highlighting their significance over conventional DDS. Later sections of the review are focused on the current status of clinical trials and future implications of CPP-based PDCs in vaccine development. KEY POINTS: • Cell-penetrating peptides (CPPs) can deliver a variety of cargo macromolecules via covalent and non-covalent conjugation. • CPP-based peptide drug conjugates (PDCs) can overcome drawbacks of conventional drug delivery methods such as biocompatibility, solubility, stability, and specificity. • Various PDCs are in clinical trial phase for cancer and ocular therapeutics.

Dataset Information

A current perspective on applications of macrocyclic-peptide-based high-affinity ligands.

Publications

A current perspective on applications of macrocyclic-peptide-based high-affinity ligands.

Similar Datasets

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