Sustainability Challenges in Peptide Synthesis and Purification: From R&D to Production

被引:318
作者
Isidro-Llobet, Albert [1 ]
Kenworthy, Martin N. [2 ]
Mukherjee, Subha [3 ]
Kojach, Michael E. [4 ]
Wegner, Katarzyna [5 ]
Gallou, Fabrice [6 ]
Smith, Austin G. [7 ]
Roschangar, Frank [8 ]
机构
[1] GlaxoSmithKline, Med Res Ctr, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England
[2] AstraZeneca, Pharmaceut Technol & Dev, Silk Rd,Business Pk,Charter Way, Macclesfield SK10 2NA, Cheshire, England
[3] Bristol Myers Squibb Co, Chem & Synthet Dev, One Squibb Dr, New Brunswick, NJ 08903 USA
[4] Eli Lilly & Co, Small Mol Design & Dev, 1400 West Raymond St, Indianapolis, IN 46285 USA
[5] IPSEN Mfg Ireland Ltd, Act Pharmaceut Ingredient Dev, Blanchardstown Ind Pk, Dublin 15, Ireland
[6] Novartis, Chem & Analyt Dev, CH-4056 Basel, Switzerland
[7] Amgen Inc, Drug Subst Proc Dev, 1 Amgen Ctr Dr, Thousand Oaks, CA 91320 USA
[8] Boehringer Ingelheim Pharmaceut, Chem Dev, Ridgefield, CT 06877 USA
关键词
FLUOROUS MIXTURE SYNTHESIS; TOTAL CHEMICAL-SYNTHESIS; LIQUID-PHASE SYNTHESIS; CARBOXYLIC-ACIDS; STAUDINGER LIGATION; COUPLING REAGENTS; PROTEIN-SYNTHESIS; PROTECTING GROUP; GREEN CHEMISTRY; SCALE SYNTHESIS;
D O I
10.1021/acs.joc.8b03001
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
In recent years, there has been a growing interest in therapeutic peptides within the pharmaceutical industry with more than 50 peptide drugs on the market, approximately 170 in clinical trials, and >200 in preclinical development. However, the current state of the art in peptide synthesis involves primarily legacy technologies with use of large amounts of highly hazardous reagents and solvents and little focus on green chemistry and engineering. In 2016, the ACS Green Chemistry Institute Pharmaceutical Roundtable identified development of greener processes for peptide API as a critical unmet need, and as a result, a new Roundtable team formed to address this important area. The initial focus of this new team is to highlight best practices in peptide synthesis and encourage much needed innovations. In this Perspective, we aim to summarize the current challenges of peptide synthesis and purification in terms of sustainability, highlight possible solutions, and encourage synergies between academia, the pharmaceutical industry, and contract research organizations/contract manufacturing organizations.
引用
收藏
页码:4615 / 4628
页数:14
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