Accurate quantification of modified cyclic peptides without the need for authentic standards
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There is a growing interest in the use of cyclic peptides as therapeutics, but their efficient production is often the bottleneck in taking them forward in the development pipeline. We have recently developed a method to synthesise azole-containing cyclic peptides using enzymes derived from different cyanobactin biosynthetic pathways. Accurate quantification is crucial for calculation of the reaction yield and for the downstream biological testing of the products. In this study, we demonstrate the development and validation of two methods to accurately quantify these compounds in the reaction mixture and after purification. The first method involves the use of a HPLC coupled in parallel to an ESMS and an ICPMS, hence correlating the calculated sulfur content to the amount of cyclic peptide. The second method is an NMR ERETIC method for quantifying the solution concentration of cyclic peptides. These methods make the quantification of new compounds much easier as there is no need for the use of authentic standards when they are not available.
Adaba , R I , Mann , G , Raab , A , Houssen , W E , McEwan , A R , Thomas , L , Tabudravu , J , Naismith , J H & Jaspars , M 2016 , ' Accurate quantification of modified cyclic peptides without the need for authentic standards ' Tetrahedron , vol 72 , no. 52 , pp. 8603-8609 . DOI: 10.1016/j.tet.2016.11.040
© 2016 Elsevier Ltd. All rights reserved. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1016/j.tet.2016.11.040
MJ, JHN, WEH, LT gratefully acknowledge support from the the Leverhulme Trust (RPG 2012-504). JT and AR were funded by EU-FP7 project ‘PharmaSea’ (contract 312184) and ARM and GM were funded by Scottish Enterprise High Growth Spinout Programme PS7305CA38.
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