选择性氟化对胰高血糖素样肽-1生物活性及蛋白水解稳定性的影响
Influence of selective fluorination on the biological activity and proteolytic stability of glucagon-like peptide-1.
作者信息
Meng He, Krishnaji Subrahmanian Tarakkad, Beinborn Martin, Kumar Krishna
机构信息
Department of Chemistry, Tufts University, Medford, Massachusetts 02155, USA.
出版信息
J Med Chem. 2008 Nov 27;51(22):7303-7. doi: 10.1021/jm8008579.
Abstract
The relative simplicity and high specificity of peptide therapeutics has fueled recent interest. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. We report here the design, synthesis, and characterization of fluorinated analogues of the gut hormone peptide, GLP-1. Overall, fluorinated GLP-1 analogues displayed higher proteolytic stability with simultaneous retention of biological activity (efficacy). Fluorinated amino acids are useful for engineering peptide drug candidates and probing ligand-receptor interactions.
摘要
肽类疗法相对简单且特异性高，这引发了近期的关注。然而，肽类和蛋白质药物通常需要注射给药，并且代谢稳定性较低。我们在此报告肠道激素肽GLP - 1的氟化类似物的设计、合成及表征。总体而言，氟化GLP - 1类似物表现出更高的蛋白水解稳定性，同时保留了生物活性（功效）。氟化氨基酸可用于构建肽类药物候选物以及探究配体 - 受体相互作用。
相似文献
1
Influence of selective fluorination on the biological activity and proteolytic stability of glucagon-like peptide-1.选择性氟化对胰高血糖素样肽-1生物活性及蛋白水解稳定性的影响
J Med Chem. 2008 Nov 27;51(22):7303-7. doi: 10.1021/jm8008579.
2
Chemoenzymatic synthesis of glycosylated glucagon-like peptide 1: effect of glycosylation on proteolytic resistance and in vivo blood glucose-lowering activity.糖基化胰高血糖素样肽1的化学酶法合成：糖基化对蛋白水解抗性及体内降血糖活性的影响
J Am Chem Soc. 2009 May 6;131(17):6237-45. doi: 10.1021/ja900261g.
3
Synthesis and bioactivity evaluation of dipeptidyl peptidase IV resistant glucagon-like peptide-1 analogues.
Protein Pept Lett. 2010 Oct;17(10):1290-5. doi: 10.2174/092986610792231546.
4
The dimerization of glucagon-like peptide-2 MIMETIBODY™ is linked to leucine-17 in the glucagon-like peptide-2 region.GLP-2 MIMETIBODY™ 的二聚化与 GLP-2 区域的亮氨酸 17 有关。
J Mol Recognit. 2012 Mar;25(3):155-64. doi: 10.1002/jmr.2154.
5
Facile synthesis of glucagon-like peptide-1 (GLP-1) mimetics.
Adv Exp Med Biol. 2009;611:119-20. doi: 10.1007/978-0-387-73657-0_53.
6
Designing Fluorinated Proteins.设计氟化蛋白质。
Methods Enzymol. 2016;580:251-78. doi: 10.1016/bs.mie.2016.05.006. Epub 2016 Jun 24.
7
A potent α/β-peptide analogue of GLP-1 with prolonged action in vivo.一种在体内具有长效作用的强效GLP-1α/β肽类似物。
J Am Chem Soc. 2014 Sep 17;136(37):12848-51. doi: 10.1021/ja507168t. Epub 2014 Sep 5.
8
Microwave-assisted solid phase synthesis, PEGylation, and biological activity studies of glucagon-like peptide-1(7-36) amide.胰高血糖素样肽-1(7-36)酰胺的微波辅助固相合成、聚乙二醇化及生物活性研究
Bioorg Med Chem. 2008 Aug 15;16(16):7607-14. doi: 10.1016/j.bmc.2008.07.019. Epub 2008 Jul 12.
9
Search for alpha-helical propensity in the receptor-bound conformation of glucagon-like peptide-1.在胰高血糖素样肽-1的受体结合构象中寻找α-螺旋倾向。
Bioorg Med Chem. 2008 Dec 1;16(23):10106-12. doi: 10.1016/j.bmc.2008.10.006. Epub 2008 Oct 5.
10
Influence of fluorination on protein-engineered coiled-coil fibers.氟化对蛋白质工程化卷曲螺旋纤维的影响。
Biomacromolecules. 2015 Apr 13;16(4):1210-7. doi: 10.1021/bm5019062. Epub 2015 Apr 2.
引用本文的文献
1
Ribosomal translation of fluorinated non-canonical amino acids for biologically active fluorinated macrocyclic peptides.用于生物活性氟化大环肽的氟化非标准氨基酸的核糖体翻译。
Chem Sci. 2024 Aug 2;15(34):13889-98. doi: 10.1039/d4sc04061a.
2
Biodegradation of Amphipathic Fluorinated Peptides Reveals a New Bacterial Defluorinating Activity and a New Source of Natural Organofluorine Compounds.两亲性氟代肽的生物降解揭示了一种新的细菌脱氟活性和一种新的天然有机氟化合物来源。
Environ Sci Technol. 2023 Jul 4;57(26):9762-9772. doi: 10.1021/acs.est.3c01240. Epub 2023 Jun 21.
3
/Sulfono--AA peptide hybrids agonist of GLP-1R with prolonged action both and ./磺酰基 - AA 肽杂合物，是 GLP - 1R 的激动剂，具有长效作用。 （注：原文中“both and.”表述不完整，不太明确具体所指，但根据已有内容尽力翻译）
Acta Pharm Sin B. 2023 Apr;13(4):1648-1659. doi: 10.1016/j.apsb.2022.10.014. Epub 2022 Oct 21.
4
Hexafluoroisobutylation of enolates through a tandem elimination/allylic shift/hydrofluorination reaction.通过串联消除/烯丙基迁移/氢氟化反应实现烯醇盐的六氟异丁基化。
Chem Sci. 2022 Jul 20;13(33):9507-9514. doi: 10.1039/d2sc02871a. eCollection 2022 Aug 24.
5
Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue.氟化物药物在大鼠体内的给药导致肝脏和脑组织中选定蛋白质的氟化。
Int J Mol Sci. 2022 Apr 11;23(8):4202. doi: 10.3390/ijms23084202.
6
A Non-Perturbative Molecular Grafting Strategy for Stable and Potent Therapeutic Peptide Ligands.一种用于稳定且强效治疗性肽配体的非微扰分子嫁接策略。
ACS Cent Sci. 2021 Mar 24;7(3):454-466. doi: 10.1021/acscentsci.0c01237. Epub 2021 Feb 15.
7
Influence of Fluorination on Single-Molecule Unfolding and Rupture Pathways of a Mechanostable Protein Adhesion Complex.氟原子取代对机械稳定蛋白黏附复合物中单分子展开和断裂途径的影响。
Nano Lett. 2020 Dec 9;20(12):8940-8950. doi: 10.1021/acs.nanolett.0c04178. Epub 2020 Nov 16.
8
Ureidopeptide GLP-1 analogues with prolonged activity signal bias and altered receptor trafficking.具有延长活性、信号偏向和改变受体转运的脲基肽GLP-1类似物。
Chem Sci. 2019 Sep 11;10(42):9872-9879. doi: 10.1039/c9sc02079a. eCollection 2019 Nov 14.
9
O-GlcNAc Engineering of GPCR Peptide-Agonists Improves Their Stability and in Vivo Activity.O-GlcNAc 工程化 GPCR 肽激动剂可提高其稳定性和体内活性。
J Am Chem Soc. 2019 Sep 11;141(36):14210-14219. doi: 10.1021/jacs.9b05365. Epub 2019 Aug 28.
10
Impact of Substitution Registry on the Receptor-Activation Profiles of Backbone-Modified Glucagon-like Peptide-1 Analogues.取代基数据库对骨干结构修饰胰高血糖素样肽-1 类似物受体激活谱的影响。
Chembiochem. 2019 Nov 18;20(22):2834-2840. doi: 10.1002/cbic.201900300. Epub 2019 Sep 20.
本文引用的文献
1
Using fluorous amino acids to modulate the biological activity of an antimicrobial peptide.利用含氟氨基酸调节抗菌肽的生物活性。
Chembiochem. 2008 Feb 15;9(3):370-3. doi: 10.1002/cbic.200700643.
2
Antimicrobial activity and protease stability of peptides containing fluorinated amino acids.含氟氨基酸肽的抗菌活性及蛋白酶稳定性
J Am Chem Soc. 2007 Dec 19;129(50):15615-22. doi: 10.1021/ja075373f. Epub 2007 Nov 28.
3
Fluorine in pharmaceuticals: looking beyond intuition.药物中的氟：超越直觉的探索。
Science. 2007 Sep 28;317(5846):1881-6. doi: 10.1126/science.1131943.
4
Helix propensity of highly fluorinated amino acids.高度氟化氨基酸的螺旋倾向。
J Am Chem Soc. 2006 Dec 13;128(49):15556-7. doi: 10.1021/ja0640445.
5
Therapeutic peptides: technological advances driving peptides into development.治疗性肽：推动肽类药物进入研发阶段的技术进展
Curr Opin Biotechnol. 2006 Dec;17(6):638-42. doi: 10.1016/j.copbio.2006.10.002. Epub 2006 Oct 17.
6
The introduction of fluorine atoms or trifluoromethyl groups in short cationic peptides enhances their antimicrobial activity.
Bioorg Med Chem. 2006 Oct 15;14(20):6971-8. doi: 10.1016/j.bmc.2006.06.027. Epub 2006 Jun 30.
7
Novel glucagon-like peptide-1 (GLP-1) analog (Val8)GLP-1 results in significant improvements of glucose tolerance and pancreatic beta-cell function after 3-week daily administration in obese diabetic (ob/ob) mice.新型胰高血糖素样肽-1（GLP-1）类似物（Val8）GLP-1在肥胖糖尿病（ob/ob）小鼠中每日给药3周后，可显著改善糖耐量和胰腺β细胞功能。
J Pharmacol Exp Ther. 2006 Aug;318(2):914-21. doi: 10.1124/jpet.105.097824. Epub 2006 Apr 28.
8
Epidemiologic and economic consequences of the global epidemics of obesity and diabetes.肥胖症和糖尿病全球流行的流行病学及经济后果。
Nat Med. 2006 Jan;12(1):62-6. doi: 10.1038/nm0106-62.
9
A human glucagon-like peptide-1 receptor polymorphism results in reduced agonist responsiveness.一种人类胰高血糖素样肽-1受体多态性导致激动剂反应性降低。
Regul Pept. 2005 Aug 15;130(1-2):1-6. doi: 10.1016/j.regpep.2005.05.001.
10
(2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.(2R)-4-氧代-4-[3-(三氟甲基)-5,6-二氢[1,2,4]三唑并[4,3-a]吡嗪-7(8H)-基]-1-(2,4,5-三氟苯基)丁-2-胺：一种用于治疗2型糖尿病的强效口服活性二肽基肽酶IV抑制剂。
J Med Chem. 2005 Jan 13;48(1):141-51. doi: 10.1021/jm0493156.
Zotero 插件