Comparison of Alternative Piperidine Deblocking Agents in Solid-Phase Synthesis of Ingramon and Methylin

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The work is devoted to the comparison of alternative piperidine deblocking agents using the examples of solid-phase synthesis of ingramon, which has anti-inflammatory activity, and methylin, an agonist of the transmembrane API receptor. The possibility of using these peptides for the treatment of cardiovascular diseases dictates the need to develop optimized methods for their synthesis. Particular attention in the work is paid to the choice of a reagent for removing Fmoc protection in solid-phase peptide synthesis, which would ensure a high yield and purity of the target product with a minimum amount of related impurities. In the synthesis of the aspartyl peptide ingramon, the lowest content of by-products was noted when using a mixture containing 10% piperazine for cleaving the Fmoc protection. In addition, piperazine is an accessible and low-toxic reagent, which is attractive for large-scale solid-phase peptide synthesis. In the synthesis of methylin, the maximum yield of the product was obtained using a deblocking mixture based on pyrrolidine. The selected deblocking reagents can successfully replace toxic piperidine in solid-phase peptide synthesis not only in the laboratory but also in the preparative scale. These reagents can find application in obtaining peptide pharmaceutical substances.

作者简介

M. Klimova

Razumovsky Moscow State University of Technology and Management; Chazov National Medical Research Center of Cardiology

Email: peptide-cardio@yandex.ru
Russia, Moscow

A. Molokocdov

Chazov National Medical Research Center of Cardiology

Russia, Moscow

M. Ovchinnikov

Chazov National Medical Research Center of Cardiology

Russia, Moscow

M. Palkceva

Chazov National Medical Research Center of Cardiology

Russia, Moscow

U. Kozhokar

Chazov National Medical Research Center of Cardiology

Russia, Moscow

D. Avdeev

Chazov National Medical Research Center of Cardiology

Russia, Moscow

M. Sidorova

Chazov National Medical Research Center of Cardiology

Russia, Moscow

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