模拟肽的构象限制在药物设计中的应用

侯辉; 孙德群

doi:10.7536/PC150203

化学进展 ›› 2015, Vol. 27 ›› Issue (9) :1260-1274 DOI: 10.7536/PC150203

综述与评论

扫码查看或转发全文

模拟肽的构象限制在药物设计中的应用

侯辉, 孙德群*

作者信息 +

Conformational Restriction of Peptidomimetics in Drug Design

Hou hui, Sun Dequn*

Author information +

文章历史 +

摘要

构象限制的模拟肽具有更好的生物活性和代谢稳定性,可以作为酶和受体活性位点的多肽替代物,是重要的药物设计工具。将特定的结构引入到生物活性肽中进行构象限制就得到了模拟肽,设计合成特定结构的模拟肽,需要一些方法作为指导,这些方法可以使模拟肽按设想产生特定的生物活性而减少设计的盲目性。本文综述了模拟肽构象限制的两类方法,即模拟肽的局部构象限制和模拟肽的整体环化。通过这两种主要方式的结构改进得到的构象限制的模拟肽,对改进模拟肽的药效学和药代动力学性质起了重要作用,包括提高其生物活性、选择性、代谢的稳定性和吸收性质。

Abstract

Peptidomimetics are important drug design tools as substitutes for peptides in active sites of enzymes and receptors. The incorporation of some specific structure into biologically active peptides may lead to conformationally restricted peptidomimetics. Conformational restriction of peptidomimetics may significantly improve the pharmacodynamic properties and pharmacokinetic properties, including bioactivity, selectivity to receptors, stability of metabolism and absorption properties. To develop new approaches, allow rational design and synthesis of restricted peptidomimetics is of importance. Herein, we review two approaches to access conformationally restricted peptidomimetics, the local conformational restriction approach and the overall cyclization approach.

Contents
1 Introduction
2 Local conformational restriction of peptide
2.1 C^α-methylated amino acids
2.2 N-methylated amino acids
2.3 C^α,C^α-dialkyl amino acids
2.4 C^β,C^β-dialkyl amino acids
2.5 α,β-unsaturated amino acids
2.6 C-C cyclization of amino acids
2.7 C-N cyclization of amino acids
2.8 N-N cyclization of amino acids
3 The overall cyclization of peptides
3.1 The overall cyclization methods of peptides
3.2 Other cyclization methods expect lactam bond
4 Conclusion

Graphical abstract

关键词

药物设计 / 模拟肽 / 构象限制 / 生物活性 / 代谢稳定性

Key words

drug design / peptidomimetics / conformational restriction / bioactivity / metabolic stability

引用本文

引用格式 ▾

侯辉, 孙德群. 模拟肽的构象限制在药物设计中的应用[J]. 化学进展, 2015, 27(9): 1260-1274 DOI:10.7536/PC150203

Hou hui, Sun Dequn. Conformational Restriction of Peptidomimetics in Drug Design[J]. Progress in Chemistry, 2015, 27(9): 1260-1274 DOI:10.7536/PC150203

登录浏览全文

4963

注册一个新账户忘记密码

参考文献

原文顺序 | 出版日期 | 本文引用

[1] Vlieghe P, Lisowski V, Martinez J, Khrestchatisky M. Drug Discovery Today, 2010, 15(1/2): 40.
[2] Craik D J, Fairlie D P, Liras S. Chem. Biol. Drug Des., 2013, 81(1): 136.
[3] Wood M P, Cole1 A L, Ruchala P, Waring A J, Rohan L C, Marx P, Tarwater P M, Gupta P, Cole A M. PLoS One, 2013, 8(2): 1.
[4] Crisma M, Formaggio F, Toniolo C, Yoshikawa T, Wakamiya T. J. Am. Chem. Soc., 1999, 121: 3272.
[5] Pirat C, Farce A, Lebègue N, Renault N, Furman C, Millet R, Yous S, Speca S, Berthelot P. J. Med. Chem., 2012, 55: 4027.
[6] Olson G L, Bolin D R, Bonner M P. J. Med. Chem., 1993, 36: 3039.
[7] Mills F D, Antharam V C, Ganesh O K, Elliott D W, McNeill S A, Long J R. Biochemistry, 2008, 47: 8292.
[8] Demirev P A. Anal. Chem., 2013, 85: 779.
[9] Chang L C, Yang C Y, Chu A C N, Lin Y J, Lai S M. Pharmaceutics, 2011, 8: 1767.
[10] Han J, Sun L D, Chu Y Y, Li Z, Huang D D, Zhu X Y. J. Med. Chem., 2013, 56: 9955.
[11] Bausch D, Thomas S, Mino-Kenudson M, Castillo C F, Bauer T W, Williams M, Warshaw A L, Thayer S P, Kelly K A. Clin. Cancer Res., 2011, 17(2): 302.
[12] Jung K H, Angela H S, Stanley A T. Molecular pharmacology, 2011, 80(3): 357.
[13] 周家驹(Zhou J J), 雷静(Lei J), 谢桂荣(Xie G R). 化学进展(Progress in Chemistry), 2000, 12(2/3): 332.
[14] Karle Z L, Flppen-Anderson J L, Uma K, Balaram P. Biopolymers, 1990, 29(14): 1835.
[15] Toniolo C, Crisma M, Formaggio F, Valle C, Cavicchioni G, Precigoux G, Aubry A, Kamphuis J. Biopolymers, 1993, 33 (7): 1061.
[16] Dehner A, Planker E, Gemmecker G, Broxterman Q B, Bisson W, Formaggio F, Crisma M, Toniolo C, Kessler H. J. Am. Chem. Soc., 2001, 123: 6678.
[17] Dechantsreiter M A, Planker E, Matha B, Lohof E, Kessler H. J. Med. Chem., 1999, 42: 3033.
[18] Chatterjee J, Ovadia O, Zahn G, Marinelli L, Hoffman A, Gilon C, Kessler H. J. Med. Chem., 2007, 50: 5878.
[19] Nowick S S. Acc. Chem.Res., 2008, 41: 1319.
[20] Formaggio F, Crisma M, Toniolo C. Macromolecules, 2003, 36: 8164.
[21] Evans M C, Pradhan A, Venkatraman S, Ojala W H, Gleason W B, Mishra R K, Johnson R L. J. Med. Chem., 1999, 42: 1441.
[22] Kruszynski M, Lammek B, Manning M. J. Med. Chem., 1980, 23: 364.
[23] Baldisserotto A, Ferretti V, Destro F, Franceschini C, Marastoni M, Gavioli R, Tomatis R. J. Med. Chem., 2010, 53: 6511.
[24] Subasinghe N, Schulte M, Chan M Y M, Roon R J, Koerner J F, Johnsony R L. J. Med. Chem., 1990, 33: 2734.
[25] Cativiela C, Fraile J M, Mayoral J A. Bull. Chem. Soc. Jpn., 1990, 63(8): 2456.
[26] Jimenez A I, Cativiela C, Marraud M. Tetrahedron, 2000, 5353.
[27] 张刘生(Zhang L S), 潘成学(Pan C X). 广西师范大学学报(Journal of Guangxi Normal University), 2011, 29(3): 37.
[28] Naiema M, Julien D, Bruno C, Laurence V B, Nicole B Sandrine O, Fariza R, Michele R R, Sames S. J. Med. Chem., 2004, 47: 6392.
[29] Martin S F, Dorsey G O, Gane T, Hillier M C. J. Med. Chem., 1998, 41: 1581.
[30] Schiller P W, Weltrowska G, Nguyen T M D, Lemieux C, Chung N N, Marsden B J, Wilkes B C. J. Med. Chem., 1991, 34: 3125.
[31] Yamazaki T, Zhu Y F, Probstl A, Chadha R K, Goodman M. J. Org. Chem., 1991, 56: 6644.
[32] Kyle D J, Hicks R P, Blake P R, Klimkowski V J. Inflammatory Disease and Therapy,1990, 5: 131.
[33] Kyle D J, Martin J A, Burch R M, Carter J P, Lu S F, Meeker S, Prosser J C, Sullivan J P, Togo J. J. Med. Chem., 1991, 34: 2649.
[34] Ji H T, Gomez-Vidal J A, Martasek P, Roman L J, Silverman R B. J. Med. Chem., 2006, 49: 6254.
[35] Fulda S, Wick W, Weller M, Debati K M. Nat. Med., 2002, 8: 808.
[36] Arn C R, Chiorean M V, Heldebrant M P, Gores G J, Kaufmann S H. J. Biol. Chem., 2002, 277: 44236.
[37] Yang L, Mashima T, Sato S, Mochizuki M, Sakamoto H, Yamori T, Oh-Hara T, Tsuruo T. Cancer Res., 2003, 63: 831.
[38] Sun H Y, Nikolovska-Coleska Z, Yang C Y, Xu L, Liu M L, Tomita Y, Pan H G, Yoshioka Y,Krajewski K, Roller P P, Wang S M. J. Am. Chem. Soc., 2004, 126: 16686.
[39] Sun H Y, Lu J F, Liu L, Yang C Y, Wang S M. ACS Chem. Biol., 2014, 9: 994.
[40] Mandal P K, Gao F Q, Lu Z, Ren Z Y, Ramesh R, Birtwistle J S, Kaluarachchi K K, Chen X M, Liao W S, McMurray J S. J. Med. Chem., 2011, 54: 3549.
[41] Miller S M, Simon R J, Ng S, Zuckermann R N, Kerr J M, Moos W H. Drug Develop. Res., 1995, 35(1): 20.
[42] Suwai S, Kodadek T. Org. Biomol. Chem., 2013, 11: 2088.
[43] Ventosa-Andrés P, Hradilova L , Krch Dň ák V. ACS Comb. Sci., 2014, 16: 359.
[44] Dubbelboer I R, Lilienberg E, Hedeland M, Bondesson U, Piquette-Miller M. Mol. Pharmaceutics, 2014, 11: 1301.
[45] Grotenbreg G M, Kronemeijer M, Timmer M S M, Oualid F E, Verdoes M, Spalburg E. J. Org. Chem., 2004, 69: 7851.
[46] Cardenas F, Thormann M, Feliz M, Caba J M, Lloyd-WillIams P, Giralt E. J. Org. Chem., 2001, 66: 4580.
[47] Dimaio J, Nguyen T M D, Lenieux C. J. Med. Chem., 1982, 25: 1432.
[48] Mosberg H I, Hurst R, Hruby V J. Life Sci., 1983, 32: 2565.
[49] Nam N H, Ye G F, Sun G Q, Parang K. J.Med.Chem., 2004, 47: 3131.
[50] Mendel S J. Clin. Cancer Res., 1997, 3(12): 2703.
[51] Sleuijfer S, Coquard R I, Papai Z J. Clin. Oncol., 2009, 27(19): 3126.
[52] Chamrád I, Rix U, Stukalov A, Gridling M, Parapatics K, Müller A, Altiok S, Colinge J, Superti-Furga G, Haura E B, Bennett K L. J. Proteome Res., 2013, 12: 4005.
[53] Schiller P W.Peptides, 1984, 6: 219.
[54] Wynants C, Bernd M, Kogler H. Tetrahedron, 1988, 44(3): 941.
[55] Figliozzi G M, Goldsmith R, Banville S C. Methods in Enzymology, 1996, 267: 437.
[56] Patch J A, Barron A E. J. Am. Chem. Soc., 2005, 25: 12092.
[57] Shin S B Y, Yoo B, Todaro L J, Kirshenbaum K. J. Am. Chem. Soc., 2007, 129(11): 3218.
[58] Dutton F E, Lee B H, Johnson S S, Coscarelli E M, Lee P H. J. Med. Chem., 2003, 46: 2057.
[59] Montero A, Beierle J M, Olsen C A, Ghadiri M R. J. Am. Chem.Soc., 2009, 131: 3033.
[60] Tahoori F, Balalaie S, Sheikhnejad R, Sadjadi M, Boloori P. Amino Acid, 2014, 46(4): 1033.
[61] Gerona-Navarro G, Yoel-Rodríguez, Mujtaba S, Frasca A, Patel J, Zeng L, Plotnikov A N, Osman R, Zhou M M. J. Am. Chem. Soc., 2011, 133: 2040.
[62] Yurek-George A, Cecil A R L, Mo A H K, Wen S J, Rogers H, Habens F,Maeda S, Yoshida M, Packham G, Ganesan A. J. Med. Chem., 2007, 50: 5720.
[63] Almeida A M, Li R, Gellman S H. J. Am. Chem. Soc., 2012, 134: 75.
[64] Johannesson P, Lindeberg G, Tong W M, Gogoll A, Synnergren B, Nyberg F, Karlen A, Hallberg A. J. Med. Chem., 1999, 42: 4524.
[65] Bailey K L, Molinski T F. J. Org. Chem., 1999, 64: 2500.
[66] Kase H, Kaneko M, Yamada K. J. Antibiot., 1987, 40: 450.
[67] Sano S, Ikai K, Kuroda H, Nakamura T, Obayashi A, Ezure Y, Enomoto H. J. Antibiot., 1986, 39: 1674.
[68] Pessah I N, Molinski T F, Meloy T D, Wong P, Buck E D, Allen P D, Mohr F C, Mack M M. Am. J. Physiol., 1997, 41: C601.
[69] Johannesson P, Lindeberg G, Johansson A, Nikiforovich G V, Gogoll A, Synnergren B, Greves M L, Nyberg F, Kerlen A, Hallerg A. J. Med. Chem., 2002, 45: 1767.
[70] Light A. Proteins, Structure and Function. Englewood Cliffs NJ:Prentice-Hall Inc. 1975.
[71] Murugavel R, Choudhury A, Walawalkar M G, Pothiraja R, Rao C N R. Chem. Rev., 2008, 108: 3549.
[72] Michele G, Raphaeel D. WO 2012123928 A1 20120920, 2012.
[73] Van Oijen A H, Erkelens C, van Boom J H, Liskamp R M J. J. Am. Chem. Soc., 1989, 111: 9103.
[74] Wu Y L, Kohn J. J. Am. Chem. Soc., 1991, 113: 687.
[75] Davies J S, Tremeer E J. J. Chem. Soc., 1987, 5: 1099.
[76] Thairivongs S, Blinn R J, Pal D T. J. Med. Chem.,1991, 34: 1276.
[77] Robinson J A. Acc. Chem.Res., 2008, 41: 1278.
[78] Patgiri A, Jochim A L, Arora P S. Acc. Chem. Res. 2008, 41: 1289.
[79] Bernal F, Tyler A F, Korsmeyer S J, Walensky L D, Verdine G L. J. Am. Chem. Soc., 2007, 129: 2456.
[80] Walensky L D, Bird G H. J. Med. Chem., 2014, 57: 6275.
[81] Bird G H, Gavathiotis E, LaBelle J L, Katz S G, Walensky L D. ACS Chem. Biol., 2014, 9: 831.
[82] Spokoyny A M, Zou Y K, Ling J J,Yu H T, Lin Y S, Pentelute B L. J. Am. Chem. Soc., 2013, 135: 5946.
[83] Brown S P, Smith A B. J. Am. Chem. Soc., 2015, 137: 4034.