Antibody mimetic explained

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.^[1]

Examples

Antibody mimetic	Scaffold	Molar mass	Example drug
Affibody molecules^[2]		6 kDa	ABY-025
Affilins^[3]		20 kDa
		10 kDa	SPVF 2801
Affimers^[4] (Adhirons)		12–14 kDa
Affitins^[5]	Sac7d (from Sulfolobus acidocaldarius)	7 kDa
Alphabodies^[6]		10 kDa	CMPX-1023
Anticalins^[7]	Lipocalins	20 kDa
Avimers^[8]	A domains of various membrane receptors	9–18 kDa
DARPins^[9]	Ankyrin repeat motif	10–19 kDa	MP0112
Fynomers^[10]		7 kDa
Gastrobodies^[11]		20 kDa
Kunitz domain peptides^[12]	Kunitz domains of various protease inhibitors	6 kDa	Ecallantide (Kalbitor)
Monobodies^[13]		10 kDa	Pegdinetanib (Angiocept)
nanoCLAMPs^[14]	Carbohydrate Binding Module 32-2 (from Clostridium perfringens NagH)	16 kDa
Optimers^[15]	Flexible nucleic acid based scaffold; G-quadruplex	8-15 kDa
Repebodies^[16]	leucine-rich repeats
Pronectin™^[17]	fourteenth fibronectin type-III scaffold  of Human Fibronectin (14Fn3)	10 kDa
Centyrins^[18]	highly stable fibronectin type III (FN3) domain	10 kDa
Obodies^[19]	a high affinity binding protein domain engineered to bind to Hen Egg-white Lysozyme

See also

• Protein mimetic
• Optimer Ligand

Notes and References

1. Gebauer M, Skerra A . Engineered protein scaffolds as next-generation antibody therapeutics . Curr Opin Chem Biol . 13. 3. 245–255. June 2009 . 19501012 . 10.1016/j.cbpa.2009.04.627 .
2. Nygren PA . Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle scaffold . FEBS J. . 275 . 11 . 2668–76 . June 2008 . 18435759 . 10.1111/j.1742-4658.2008.06438.x . free .
3. Ebersbach H, Fiedler E, Scheuermann T . Affilin-novel binding molecules based on human gamma-B-crystallin, an all beta-sheet protein . J. Mol. Biol. . 372 . 1 . 172–85 . September 2007 . 17628592 . 10.1016/j.jmb.2007.06.045 . etal.
4. Johnson A, Song Q, Ko Ferrigno P, Bueno PR, Davis JJ . Sensitive Affimer and antibody based impedimetric label-free assays for C-reactive protein. Anal. Chem.. Aug 7, 2012. 84. 6553–60. 22789061. 10.1021/ac300835b. 15.
5. Krehenbrink M, Chami M, Guilvout I, Alzari PM, Pécorari F, Pugsley AP . Artificial binding proteins (Affitins) as probes for conformational changes in secretin PulD . J. Mol. Biol. . 383 . 5 . 1058–68 . November 2008 . 18822295 . 10.1016/j.jmb.2008.09.016 .
6. Desmet J, Verstraete K, Bloch Y, Lorent E, Wen Y, Devreese B, Vandenbroucke K, Loverix S, Hettmann T, Deroo S, Somers K, Henderikx P, Lasters I, Savvides SN . 6 . Structural basis of IL-23 antagonism by an Alphabody protein scaffold . Nature Communications . 5 . 5237 . October 2014 . 25354530 . 4220489 . 10.1038/ncomms6237 .
7. Skerra A . Alternative binding proteins: anticalins - harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities . FEBS J. . 275 . 11 . 2677–83 . June 2008 . 18435758 . 10.1111/j.1742-4658.2008.06439.x . 19992238 . free .
8. Silverman J, Liu Q, Lu Q . Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains . Nat. Biotechnol. . 23 . 12 . 1556–61 . December 2005 . 16299519 . 10.1038/nbt1166 . 84757398 . etal.
9. Stumpp MT, Binz HK, Amstutz P . DARPins: a new generation of protein therapeutics . Drug Discov. Today . 13 . 15–16 . 695–701 . August 2008 . 18621567 . 10.1016/j.drudis.2008.04.013 .
10. Grabulovski D, Kaspar M, Neri D . A novel, non-immunogenic Fyn SH3-derived binding protein with tumor vascular targeting properties . The Journal of Biological Chemistry . 282 . 5 . 3196–204 . February 2007 . 17130124 . 10.1074/jbc.M609211200 . free .
11. Wicke N, Bedford MR, Howarth M . Gastrobodies are engineered antibody mimetics resilient to pepsin and hydrochloric acid . Communications Biology . 4 . 1 . 960 . August 2021 . 34381153 . 10.1038/s42003-021-02487-2 . 8358037 . free .
12. Nixon AE, Wood CR . Engineered protein inhibitors of proteases . Curr Opin Drug Discov Dev . 9 . 2 . 261–8 . March 2006 . 16566296 .
13. Book: Koide A, Koide S . Protein Engineering Protocols . Monobodies: antibody mimics based on the scaffold of the fibronectin type III domain . Methods Mol. Biol. . 352 . 95–109 . 2007 . 17041261 . 10.1385/1-59745-187-8:95. 978-1-59745-187-1 .
14. Suderman RJ, Rice DA, Gibson SD, Strick EJ, Chao DM . Development of polyol-responsive antibody mimetics for single-step protein purification . Protein Expression and Purification . 134 . 114–124 . April 17, 2017 . 10.1016/j.pep.2017.04.008 . 28428153. free .
15. Web site: Rapid identification and development of SARS-CoV-2 selective Optimers . Aptamer Group . 11 December 2020 . 2021-08-03.
16. Hantschel O . Monobodies as possible next-generation protein therapeutics - a perspective . Swiss Medical Weekly . 147 . 4748 . w14545 . 2017-11-20 . 29185244 . 7316567 . 10.4414/smw.2017.14545 .
17. Web site: Pronectin Technology. 2021-09-26. Protelica. en.
18. Goldberg SD, Cardoso RM, Lin T, Spinka-Doms T, Klein D, Jacobs SA, Dudkin V, Gilliland G, O'Neil KT . 6 . Engineering a targeted delivery platform using Centyrins . Protein Engineering, Design & Selection . 29 . 12 . 563–572 . December 2016 . 27737926 . 10.1093/protein/gzw054 . free .
19. Engineering and characterisation of anti-progesterone OBodies. The University of Waikato. 2018. Thesis. en . Chonira VK .