A Four-Legged Lottery

Why Tweaked Peptides Can’t Be Picked Up in Swabs – Part 2 – The Cheats Tweak Them Too Quick

The analysis of prohibited substances used to improve athletic performance is an analytical challenge that requires the continuous optimization of methodologies in terms of sensitivity, precision, accuracy, recovery rate, decrease in the number of false positives, and analysis time, among others.

The role of peptides in research focused on antidoping presents extensive challenges for the future, mainly because it is necessary to obtain reference materials that allow the continuous development of analytical methodologies for their adequate detection.

Although many efforts have been made in this field, the chemical synthesis of peptides has been a relatively unexplored area.

Therefore, we believe that solid-phase peptide synthesis (SPPS) using the Fmoc/tBu strategy can be an important alternative for obtaining in-house reference materials with high percentages of yield and purity, which could be an additional step in the fight against doping, and that it would be suitable for the routine analysis of peptides with possible use as a doping agent.

The detection and/or quantification of synthetic peptides used in doping poses an additional analytical challenge due to factors such as emergence of new peptides, very short lifetimes, and low concentrations in the body, and they can mimic naturally produced molecules, trigger biological processes indirectly, etc.

Although significant progress has been made in the pre-treatment of samples and the instrumentation, which has allowed the development of more sensitive, precise, and accurate analytical methods, there are still some aspects that need improvement, such as detection and quantification of peptides with low concentrations in complex matrices and identification and characterization of biomarkers, especially for peptides with short half-lives, to obtain reference materials, especially those synthesized at home, in order to create strategies for the rapid detection of peptides, which are continually entering the doping market, among others.

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