拟抗体
拟抗体是一种功能与抗体类似，但结构与之完全没有任何关系的有机化合物，它可以与抗原特异结合。通常它是人造的肽或者蛋白质，摩尔质量介于3至20kDa之间。有些氨基酸和小分子也被认为是拟抗体，而不是人造抗体、抗体结合区段或者融合蛋白的一部分。某些拟抗体具有和抗体类似的β折叠结构。拟抗体相对于抗体来说，通常都具有更好的溶解性，组织穿透能力，更好的热稳定性和酶稳定性，以及相对较低的生产成本。拟抗体正被开发用于治疗与医学诊断上[1]。
示例
| 类型 | 原型 | 分子量 | 药品举例 |
|---|---|---|---|
| 亲和配体分子[2] | A蛋白Z域 | 6 kDa | ABY-025 |
| Affilin[3] | 乙型γ晶状体蛋白 | 20 kDa | |
| 泛素 | 10 kDa | SPVF 2801 | |
| Affitin[4] | Sac7d (from Sulfolobus acidocaldarius) | 7 kDa | |
| 载脂蛋白拟抗体[5] | Lipocalins | 20 kDa | |
| 亲和性多聚体[6] | A domains of various membrane receptors | 9–18 kDa | |
| 人造锚重复蛋白[7] | Ankyrin repeat motif | 10–19 kDa | MP0112 |
| 原癌基因酪氨酸蛋白激酶多聚体[8] | 原癌基因酪氨酸蛋白激酶的SH3域 | 7 kDa | |
| Kunitz型结构域肽[9] | 多种蛋白酶抑制剂的Kunitz域 | 6 kDa | Ecallantide |
| 单拟抗体[10] | 纤连蛋白的第10个3型域 | 10 kDa | Angiocept |
引用
- ^ Gebauer M, Skerra A. Engineered protein scaffolds as next-generation antibody therapeutics. Curr Opin Chem Biol. June 2009, 13 (3): 245–255 [2011-09-14]. PMID 19501012. doi:10.1016/j.cbpa.2009.04.627. （原始内容存档于2019-11-29）.
- ^ Nygren PA. Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle scaffold. FEBS J. June 2008, 275 (11): 2668–76. PMID 18435759. doi:10.1111/j.1742-4658.2008.06438.x.
- ^ Ebersbach H, Fiedler E, Scheuermann T; et al. Affilin-novel binding molecules based on human gamma-B-crystallin, an all beta-sheet protein. J. Mol. Biol. September 2007, 372 (1): 172–85. PMID 17628592. doi:10.1016/j.jmb.2007.06.045.
- ^ 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. November 2008, 383 (5): 1058–68 [2011-09-14]. PMID 18822295. doi:10.1016/j.jmb.2008.09.016. （原始内容存档于2019-11-30）.
- ^ Skerra A. Alternative binding proteins: anticalins - harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities. FEBS J. June 2008, 275 (11): 2677–83. PMID 18435758. doi:10.1111/j.1742-4658.2008.06439.x.
- ^ Silverman J, Liu Q, Lu Q; et al. Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains. Nat. Biotechnol. December 2005, 23 (12): 1556–61. PMID 16299519. doi:10.1038/nbt1166.
- ^ Stumpp MT, Binz HK, Amstutz P. DARPins: a new generation of protein therapeutics. Drug Discov. Today. August 2008, 13 (15–16): 695–701 [2011-09-14]. PMID 18621567. doi:10.1016/j.drudis.2008.04.013. （原始内容存档于2019-12-01）.
- ^ Grabulovski D; Kaspar, M; Neri, D. A novel, non-immunogenic Fyn SH3-derived binding protein with tumor vascular targeting properties. J Biol Chem. 2007, 282 (5): 3196–3204. PMID 17130124. doi:10.1074/jbc.M609211200.
- ^ Nixon AE, Wood CR. Engineered protein inhibitors of proteases. Curr Opin Drug Discov Devel. March 2006, 9 (2): 261–8. PMID 16566296.
- ^ Koide A, Koide S. Monobodies: antibody mimics based on the scaffold of the fibronectin type III domain. Methods Mol. Biol. 2007, 352: 95–109. PMID 17041261.