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.^[1]

Examples

Antibody mimetic	Scaffold	Molar mass	Example drug
Affibody molecules^[2]	Z domain of Protein A	6 kDa	ABY-025
Affilins^[3]	Gamma-B crystallin	20 kDa
Affilins^[3]	Ubiquitin	10 kDa	SPVF 2801
Affimers^[4] (Adhirons)	Cystatin	12–14 kDa
Affitins^[5]	Sac7d (from Sulfolobus acidocaldarius)	7 kDa
Alphabodies^[6]	Triple helix coiled coil	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]	SH3 domain of Fyn	7 kDa
Gastrobodies^[11]	Kunitz-type soybean trypsin inhibitor	20 kDa
Kunitz domain peptides^[12]	Kunitz domains of various protease inhibitors	6 kDa	Ecallantide (Kalbitor)
Monobodies^[13]	10th type III domain of fibronectin	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

References

^ Gebauer M, Skerra A (June 2009). "Engineered protein scaffolds as next-generation antibody therapeutics". Curr Opin Chem Biol. 13 (3): 245–255. doi:10.1016/j.cbpa.2009.04.627. PMID 19501012.
^ Nygren PA (June 2008). "Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle scaffold". FEBS J. 275 (11): 2668–76. doi:10.1111/j.1742-4658.2008.06438.x. PMID 18435759.
^ Ebersbach H, Fiedler E, Scheuermann T, et al. (September 2007). "Affilin-novel binding molecules based on human gamma-B-crystallin, an all beta-sheet protein". J. Mol. Biol. 372 (1): 172–85. doi:10.1016/j.jmb.2007.06.045. PMID 17628592.
^ Johnson A, Song Q, Ko Ferrigno P, Bueno PR, Davis JJ (Aug 7, 2012). "Sensitive Affimer and antibody based impedimetric label-free assays for C-reactive protein". Anal. Chem. 84 (15): 6553–60. doi:10.1021/ac300835b. PMID 22789061.
^ Krehenbrink M, Chami M, Guilvout I, Alzari PM, Pécorari F, Pugsley AP (November 2008). "Artificial binding proteins (Affitins) as probes for conformational changes in secretin PulD". J. Mol. Biol. 383 (5): 1058–68. doi:10.1016/j.jmb.2008.09.016. PMID 18822295.
^ Desmet J, Verstraete K, Bloch Y, Lorent E, Wen Y, Devreese B, et al. (October 2014). "Structural basis of IL-23 antagonism by an Alphabody protein scaffold". Nature Communications. 5: 5237. doi:10.1038/ncomms6237. PMC 4220489. PMID 25354530.
^ Skerra A (June 2008). "Alternative binding proteins: anticalins - harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities". FEBS J. 275 (11): 2677–83. doi:10.1111/j.1742-4658.2008.06439.x. PMID 18435758. S2CID 19992238.
^ Silverman J, Liu Q, Lu Q, et al. (December 2005). "Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains". Nat. Biotechnol. 23 (12): 1556–61. doi:10.1038/nbt1166. PMID 16299519. S2CID 84757398.
^ Stumpp MT, Binz HK, Amstutz P (August 2008). "DARPins: a new generation of protein therapeutics". Drug Discov. Today. 13 (15–16): 695–701. doi:10.1016/j.drudis.2008.04.013. PMID 18621567.
^ Grabulovski D, Kaspar M, Neri D (February 2007). "A novel, non-immunogenic Fyn SH3-derived binding protein with tumor vascular targeting properties". The Journal of Biological Chemistry. 282 (5): 3196–204. doi:10.1074/jbc.M609211200. PMID 17130124.
^ Wicke N, Bedford MR, Howarth M (August 2021). "Gastrobodies are engineered antibody mimetics resilient to pepsin and hydrochloric acid". Communications Biology. 4 (1): 960. doi:10.1038/s42003-021-02487-2. PMC 8358037. PMID 34381153.
^ Nixon AE, Wood CR (March 2006). "Engineered protein inhibitors of proteases". Curr Opin Drug Discov Dev. 9 (2): 261–8. PMID 16566296.
^ Koide A, Koide S (2007). "Monobodies: antibody mimics based on the scaffold of the fibronectin type III domain". Protein Engineering Protocols. Methods Mol. Biol. Vol. 352. pp. 95–109. doi:10.1385/1-59745-187-8:95. ISBN 978-1-59745-187-1. PMID 17041261.
^ Suderman RJ, Rice DA, Gibson SD, Strick EJ, Chao DM (April 17, 2017). "Development of polyol-responsive antibody mimetics for single-step protein purification". Protein Expression and Purification. 134: 114–124. doi:10.1016/j.pep.2017.04.008. PMID 28428153.
^ "Rapid identification and development of SARS-CoV-2 selective Optimers". Aptamer Group. 11 December 2020. Retrieved 2021-08-03.
^ Hantschel O (2017-11-20). "Monobodies as possible next-generation protein therapeutics - a perspective". Swiss Medical Weekly. 147 (4748): w14545. doi:10.4414/smw.2017.14545. PMC 7316567. PMID 29185244.
^ "Pronectin Technology". Protelica. Retrieved 2021-09-26.
^ Goldberg SD, Cardoso RM, Lin T, Spinka-Doms T, Klein D, Jacobs SA, et al. (December 2016). "Engineering a targeted delivery platform using Centyrins". Protein Engineering, Design & Selection. 29 (12): 563–572. doi:10.1093/protein/gzw054. PMID 27737926.
^ Chonira VK (2018). Engineering and characterisation of anti-progesterone OBodies (Thesis thesis). The University of Waikato.

[1] Gebauer M, Skerra A (June 2009). "Engineered protein scaffolds as next-generation antibody therapeutics". Curr Opin Chem Biol. 13 (3): 245–255. doi:10.1016/j.cbpa.2009.04.627. PMID 19501012.

[pmid18435759-2] Nygren PA (June 2008). "Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle scaffold". FEBS J. 275 (11): 2668–76. doi:10.1111/j.1742-4658.2008.06438.x. PMID 18435759.

[3] Ebersbach H, Fiedler E, Scheuermann T, et al. (September 2007). "Affilin-novel binding molecules based on human gamma-B-crystallin, an all beta-sheet protein". J. Mol. Biol. 372 (1): 172–85. doi:10.1016/j.jmb.2007.06.045. PMID 17628592.

[4] Johnson A, Song Q, Ko Ferrigno P, Bueno PR, Davis JJ (Aug 7, 2012). "Sensitive Affimer and antibody based impedimetric label-free assays for C-reactive protein". Anal. Chem. 84 (15): 6553–60. doi:10.1021/ac300835b. PMID 22789061.

[pmid18822295-5] Krehenbrink M, Chami M, Guilvout I, Alzari PM, Pécorari F, Pugsley AP (November 2008). "Artificial binding proteins (Affitins) as probes for conformational changes in secretin PulD". J. Mol. Biol. 383 (5): 1058–68. doi:10.1016/j.jmb.2008.09.016. PMID 18822295.

[Desmet2014-6] Desmet J, Verstraete K, Bloch Y, Lorent E, Wen Y, Devreese B, et al. (October 2014). "Structural basis of IL-23 antagonism by an Alphabody protein scaffold". Nature Communications. 5: 5237. doi:10.1038/ncomms6237. PMC 4220489. PMID 25354530.

[pmid18435758-7] Skerra A (June 2008). "Alternative binding proteins: anticalins - harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities". FEBS J. 275 (11): 2677–83. doi:10.1111/j.1742-4658.2008.06439.x. PMID 18435758. S2CID 19992238.

[pmid16299519-8] Silverman J, Liu Q, Lu Q, et al. (December 2005). "Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains". Nat. Biotechnol. 23 (12): 1556–61. doi:10.1038/nbt1166. PMID 16299519. S2CID 84757398.

[pmid18621567-9] Stumpp MT, Binz HK, Amstutz P (August 2008). "DARPins: a new generation of protein therapeutics". Drug Discov. Today. 13 (15–16): 695–701. doi:10.1016/j.drudis.2008.04.013. PMID 18621567.

[PMID_17130124-10] Grabulovski D, Kaspar M, Neri D (February 2007). "A novel, non-immunogenic Fyn SH3-derived binding protein with tumor vascular targeting properties". The Journal of Biological Chemistry. 282 (5): 3196–204. doi:10.1074/jbc.M609211200. PMID 17130124.

[11] Wicke N, Bedford MR, Howarth M (August 2021). "Gastrobodies are engineered antibody mimetics resilient to pepsin and hydrochloric acid". Communications Biology. 4 (1): 960. doi:10.1038/s42003-021-02487-2. PMC 8358037. PMID 34381153.

[pmid16566296-12] Nixon AE, Wood CR (March 2006). "Engineered protein inhibitors of proteases". Curr Opin Drug Discov Dev. 9 (2): 261–8. PMID 16566296.

[pmid17041261-13] Koide A, Koide S (2007). "Monobodies: antibody mimics based on the scaffold of the fibronectin type III domain". Protein Engineering Protocols. Methods Mol. Biol. Vol. 352. pp. 95–109. doi:10.1385/1-59745-187-8:95. ISBN 978-1-59745-187-1. PMID 17041261.

[pmid28428153-14] Suderman RJ, Rice DA, Gibson SD, Strick EJ, Chao DM (April 17, 2017). "Development of polyol-responsive antibody mimetics for single-step protein purification". Protein Expression and Purification. 134: 114–124. doi:10.1016/j.pep.2017.04.008. PMID 28428153.

[Rapid_Identification-15] "Rapid identification and development of SARS-CoV-2 selective Optimers". Aptamer Group. 11 December 2020. Retrieved 2021-08-03.

[16] Hantschel O (2017-11-20). "Monobodies as possible next-generation protein therapeutics - a perspective". Swiss Medical Weekly. 147 (4748): w14545. doi:10.4414/smw.2017.14545. PMC 7316567. PMID 29185244.

[17] "Pronectin Technology". Protelica. Retrieved 2021-09-26.

[18] Goldberg SD, Cardoso RM, Lin T, Spinka-Doms T, Klein D, Jacobs SA, et al. (December 2016). "Engineering a targeted delivery platform using Centyrins". Protein Engineering, Design & Selection. 29 (12): 563–572. doi:10.1093/protein/gzw054. PMID 27737926.

[19] Chonira VK (2018). Engineering and characterisation of anti-progesterone OBodies (Thesis thesis). The University of Waikato.

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Antibody mimetic

Examples

See also

References

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