Table 1.
Approximate sizes and a comparison of the advantages and disadvantages of the ligands discussed in this review
| Molecule | Approximate Size (kDa) | Advantages | Disadvantages |
|---|---|---|---|
| Agonist or antagonist activity | Limited penetration | ||
| Activates immune system | Limited distribution | ||
| Antibody | 150 | Conjugation to molecules (therapeutics, imaging) | Production dependent on animal immunization |
| Blocks protein–protein interactions | Costly and laborious production | ||
| High avidity due to bivalency | |||
| Intrabody | 28 | Intracellular action | Selection not amenable for transcriptional activators or repressors |
| Toxic effects of some targets, when expressed in yeast | |||
| Binds epitopes unreachable by antibodies | High uptake in liver and kidneys | ||
| Nanobody | 25 | High tissue penetration | |
| Stability in adverse environments | |||
| Single domain facilitates cloning | |||
| Monobody | 10 | Stability (thermal/reducing conditions) | High renal clearance |
| Can be constructed as multi‐domain (modularity) | |||
| High tissue penetration | High renal clearance | ||
| Can be constructed as multi‐domain (modularity) | |||
| Affibody | 8 | Can block protein‐to‐protein interactions | |
| High solubility | |||
| High stability | |||
| Can be chemically synthetized and altered | |||
| mRNA display libraries reach 1014 unique sequences | Limited delivery across cell membrane | ||
| Chemically modifiable | High renal clearance | ||
| Protease resistant | |||
| Rapid screening | |||
| Use of npAAs | |||
| Macrocyclic | 2 | High tissue penetration | |
| peptide | Ability to bind flat surfaces and pockets | ||
| Produced in animal‐ and cell‐free systems | |||
| Semi‐rigid structure | |||
| Ability to bind non‐druggable targets |