Thymosin α1 interacts with hyaluronic acid electrostatically by its terminal sequence LKEKK

Walter Mandaliti, Ridvan Nepravishta, Francesca Pica, Paola Sinibaldi Vallebona, Enrico Garaci, Maurizio Paci

Research output: Contribution to journalArticle

Abstract

Thymosin α1 (Tα1), is a peptidic hormone, whose immune regulatory properties have been demonstrated both in vitro and in vivo and approved in different countries for treatment of several viral infections and cancers. T1 assumes a conformation in negative membranes upon insertion into the phosphatidylserine exposure as found in several pathologies and in apoptosis. These findings are in agreement with the pleiotropy of T1, which targets both normal and tumor cells, interacting with multiple cellular components, and have generated renewed interest in the topic. Hyaluronan (HA) occurs ubiquitously in the extracellular matrix and on cell surfaces and has been related to a variety of diseases, and developmental and physiological processes. Proteins binding HA, among them CD44 and the Receptor for HA-mediated motility (RHAMM) receptors, mediate its biological effects. NMR spectroscopy indicated preliminarily that an interaction of T1 with HA occurs specifically around lysine residues of the sequence LKEKK of T1 and is suggestive of a possible interference of T1 in the binding of HA with CD44 and RHAMM. Further studies are needed to deepen these observations because Tα1 is known to potentiate the T-cell immunity and anti-tumor effect. The binding inhibitory activity of Tα1 on HA-CD44 or HA-RHAMM interactions can suppress both T-cell reactivity and tumor progression.

Original languageEnglish
Article number1843
JournalMolecules
Volume22
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

Keywords

  • CD44
  • RHAMM
  • Thymic hormone
  • Thymosin α1

ASJC Scopus subject areas

  • Organic Chemistry

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