Immunosuppressory activity of ubiquitin fragments containing retro-RGD sequence

Biopolymers
Zbigniew SzewczukZ Wieczorek

Abstract

A peptide fragment corresponding to the ubiquitin(50-59) sequence (LEDGRTLSDY) (U50-59) possesses a very high immunosuppressory activity, comparable to that of cyclosporine, both in the cellular and humoral immune responses. We found that the pentapeptide DGRTL (U52-56) is the shortest, effective immunosuppressory fragment of ubiquitin, although its potency is weaker than that of U50-59. Replacement of each consecutive residue with alanine in U52-56 allowed identification of essential amino acids involved in the immunosuppression. We also evaluated the roles of its N- and C-terminal groups by their acetylation and/or amidation, respectively. The active sequence is located in the external loop of the molecule and therefore it may serve as an important functional epitope for intermolecular binding. Based on the crystal structure of ubiquitin molecule, we designed and synthesized the cyclic analogue with a restricted conformation, cyclo(Glt-Gln-Leu-Glu-Asp-Gly-Arg-Thr-Leu-Ser-Asp-Lys)-NH2 (Glt = glutaryl) by reacting the C-terminal Lys side chain with the glutarylated N-terminus. The peptide was designed to mimic the ubiquitin(48-59) loop, in order to obtain the ligand that may interact with hypothetical receptors of the loop. The...Continue Reading

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Citations

Apr 9, 2008·Amino Acids·Małgorzata Koprowska-RatajskaZbigniew Szewczuk
Dec 14, 2006·Transplantation·Steven A EarleMatthias Majetschak
Mar 31, 2012·Journal of Inorganic Biochemistry·Hanna Czapor-IrzabekJustyna Brasuń
Oct 20, 2011·Peptides·Paweł PasikowskiZbigniew Szewczuk
Jul 12, 2011·Journal of Molecular Biology·Arshdeep SidhuMonica Sundd
Feb 13, 2009·Biopolymers·Lukasz JaremkoZbigniew Szewczuk
May 26, 2012·Journal of Peptide Science : an Official Publication of the European Peptide Society·Alicja KluczykZbigniew Szewczuk
May 1, 2010·Biomolecular Concepts·Paweł PasikowskiZbigniew Szewczuk
Sep 20, 2016·Mediators of Inflammation·Rusudan Sujashvili
Feb 23, 2020·Scandinavian Journal of Clinical and Laboratory Investigation·Yiqun JiYang He

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