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The solid phase synthesis of peptides containing an arginine residue with an unprotected guanidine group

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Abstract

A new variant of the solid phase synthesis of arginine-containing peptides was proposed. The conditions for the attachment to the Wang polymer of {ie235-1}-Fmoc-arginine containing a protonated guanidine group were found. We demonstrated that this attachment is accompanied by neither racemization nor the attachment of the second Arg residue. Side reactions involving the guanidine group of arginine were studied, and methods for their prevention were proposed. The comparison of the carbodiimide method with a 1-hydroxybenzotriazole additive and a modified method with the use of Kastro’s reagent for the introduction of {ie235-2}-Fmoc-Arg residue with the unprotected guanidine group into the growing peptide chain demonstrated the advantages of the second method. Bradykinin and a peptide corresponding to the 584–591 sequence of the transmembrane gp41 from HIV-1 were synthesized by the method proposed here.

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Abbreviations

Adoc:

adamantyloxycarbonyl

BOP:

1-benzotriazoleyloxy-tris(dimethylamino)phosphonium hexafluorophosphate (Kastro’s reagent)

DCC:

N,N′-dicyclohexylcarbodiimide

DIPCDI:

N,N′-diisopropylcarbodiimide

DMAP:

4-dimethylaminopyridine

HOBt:

1-hydroxybenzotriazole

EDT:

1,2-ethanedithiol

ESI MS:

the electrospray ionization mass spectrometry

Fmoc:

9-fluorenylmethyloxycabonyl

Mtr:

4-methoxy-2,3,6-trimethylbenzenesulfonyl

ONp:

p-nitrophenyl

P :

the Wang polymer

Pmc:

2,2,5,7,8-pentamethylchromane-6-sulfonyl

SPPS:

solid phase peptide synthesis

TFA:

trifluoroacetic acid

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Authors and Affiliations

  1. Russian Cardiological Research and Production Association, Ministry of Public Health of the Russian Federation, ul. Tret’ya Cherepkovskaya 15a, 121552, Moscow, Russia

    Yu. A. Rubina, Zh. D. Bespalova & V. N. Bushuev

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  1. Yu. A. Rubina
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  2. Zh. D. Bespalova
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  3. V. N. Bushuev
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Correspondence to Yu. A. Rubina.

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Rubina, Y.A., Bespalova, Z.D. & Bushuev, V.N. The solid phase synthesis of peptides containing an arginine residue with an unprotected guanidine group. Russ J Bioorg Chem 26, 235–244 (2000). https://doi.org/10.1007/BF02759162

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  • DOI: https://doi.org/10.1007/BF02759162

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