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Antibody mimetic

Antibody mimetics are organic compounds that, like antibodies, can specifically bind antigens, but that are not structurally related to antibodies. They are usually artificial peptides or proteins with a molar mass of about 3 to 20 kDa. (Antibodies are ~150 kDa.)

Nucleic acids and small molecules are sometimes considered antibody mimetics as well, but not artificial antibodies, antibody fragments and fusion proteins composed from these.

Common advantages over antibodies are better solubility, tissue penetration, stability towards heat and enzymes, and comparatively low production costs. Antibody mimetics are being developed as therapeutic and diagnostic agents.

Examples

Antibody mimeticScaffoldMolar massExample drug
author=Nygren PAtitle=Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle scaffoldjournal=FEBS J.volume=275issue=11pages=2668–76date=June 2008pmid=18435759doi=10.1111/j.1742-4658.2008.06438.xdoi-access=free }}Z domain of Protein A6 kDaABY-025
AffilinsGamma-B crystallin20 kDa
Ubiquitin10 kDaSPVF 2801
Affimers (Adhirons)Cystatin12–14 kDa
vauthors=Krehenbrink M, Chami M, Guilvout I, Alzari PM, Pécorari F, Pugsley APtitle=Artificial binding proteins (Affitins) as probes for conformational changes in secretin PulDjournal=J. Mol. Biol.volume=383issue=5pages=1058–68date=November 2008pmid=18822295doi=10.1016/j.jmb.2008.09.016 }}Sac7d (from Sulfolobus acidocaldarius)7 kDa
AlphabodiesTriple helix coiled coil10 kDaCMPX-1023
author=Skerra Atitle=Alternative binding proteins: anticalins - harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activitiesjournal=FEBS J.volume=275issue=11pages=2677–83date=June 2008pmid=18435758doi=10.1111/j.1742-4658.2008.06439.xs2cid=19992238doi-access=free }}Lipocalins20 kDa
vauthors=Silverman J, Liu Q, Lu Qtitle=Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domainsjournal=Nat. Biotechnol.volume=23issue=12pages=1556–61date=December 2005pmid=16299519doi=10.1038/nbt1166s2cid=84757398display-authors=etal}}A domains of various membrane receptors9–18 kDa
vauthors=Stumpp MT, Binz HK, Amstutz Ptitle=DARPins: a new generation of protein therapeuticsjournal=Drug Discov. Todayvolume=13issue=15–16pages=695–701date=August 2008pmid=18621567doi=10.1016/j.drudis.2008.04.013 }}Ankyrin repeat motif10–19 kDaMP0112
vauthors = Grabulovski D, Kaspar M, Neri Dtitle = A novel, non-immunogenic Fyn SH3-derived binding protein with tumor vascular targeting propertiesjournal = The Journal of Biological Chemistryvolume = 282issue = 5pages = 3196–204date = February 2007pmid = 17130124doi = 10.1074/jbc.M609211200doi-access = free }}SH3 domain of Fyn7 kDa
GastrobodiesKunitz-type soybean trypsin inhibitor20 kDa
vauthors=Nixon AE, Wood CRtitle=Engineered protein inhibitors of proteasesjournal=Curr Opin Drug Discov Devvolume=9issue=2pages=261–8date=March 2006pmid=16566296 }}Kunitz domains of various protease inhibitors6 kDaEcallantide (Kalbitor)
Monobodies10th type III domain of fibronectin10 kDaPegdinetanib (Angiocept)
vauthors = Suderman RJ, Rice DA, Gibson SD, Strick EJ, Chao DMtitle = Development of polyol-responsive antibody mimetics for single-step protein purificationjournal = Protein Expression and Purificationvolume = 134pages = 114–124date = April 17, 2017doi = 10.1016/j.pep.2017.04.008pmid = 28428153doi-access = free }}Carbohydrate Binding Module 32-2 (from Clostridium perfringens NagH)16 kDa
OptimersFlexible nucleic acid based scaffold; G-quadruplex8-15 kDa
Repebodiesleucine-rich repeats
Pronectin™fourteenth fibronectin type-III scaffold  of Human Fibronectin (14Fn3)10 kDa
Centyrinshighly stable fibronectin type III (FN3) domain10 kDa
Obodiesa high affinity binding protein domain engineered to bind to Hen Egg-white Lysozyme

References

References

  1. (June 2009). "Engineered protein scaffolds as next-generation antibody therapeutics". Curr Opin Chem Biol.
  2. Nygren PA. (June 2008). "Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle scaffold". FEBS J..
  3. (September 2007). "Affilin-novel binding molecules based on human gamma-B-crystallin, an all beta-sheet protein". J. Mol. Biol..
  4. (Aug 7, 2012). "Sensitive Affimer and antibody based impedimetric label-free assays for C-reactive protein". Anal. Chem..
  5. (November 2008). "Artificial binding proteins (Affitins) as probes for conformational changes in secretin PulD". J. Mol. Biol..
  6. (October 2014). "Structural basis of IL-23 antagonism by an Alphabody protein scaffold". Nature Communications.
  7. Skerra A. (June 2008). "Alternative binding proteins: anticalins - harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities". FEBS J..
  8. (December 2005). "Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains". Nat. Biotechnol..
  9. (August 2008). "DARPins: a new generation of protein therapeutics". Drug Discov. Today.
  10. (February 2007). "A novel, non-immunogenic Fyn SH3-derived binding protein with tumor vascular targeting properties". The Journal of Biological Chemistry.
  11. (August 2021). "Gastrobodies are engineered antibody mimetics resilient to pepsin and hydrochloric acid". Communications Biology.
  12. (March 2006). "Engineered protein inhibitors of proteases". Curr Opin Drug Discov Dev.
  13. (2007). "Protein Engineering Protocols".
  14. (April 17, 2017). "Development of polyol-responsive antibody mimetics for single-step protein purification". Protein Expression and Purification.
  15. (11 December 2020). "Rapid identification and development of SARS-CoV-2 selective Optimers".
  16. (2017-11-20). "Monobodies as possible next-generation protein therapeutics - a perspective". [[Swiss Medical Weekly]].
  17. "Pronectin Technology".
  18. (December 2016). "Engineering a targeted delivery platform using Centyrins". Protein Engineering, Design & Selection.
  19. (2018). "Engineering and characterisation of anti-progesterone OBodies". The University of Waikato.
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