title: A novel synthetic luteinizing hormone-releasing hormone (LHRH) analogue coupled with modified β-cyclodextrin: insight into its intramolecular interactions.
abstract: BACKGROUND
  Cyclodextrins (CDs) in combination with therapeutic proteins and other bioactive compounds have been proposed as candidates that show enhanced chemical and enzymatic stability, better absorption, slower plasma clearance and improved dose-response curves or immunogenicity. As a result, an important number of therapeutic complexes between cyclodextrins and bioactive compounds capable to control several diseases have been developed.
  
  
  RESULTS
  In this article, the synthesis and the structural study of a conjugate between a luteinizing hormone-releasing hormone (LHRH) analogue, related to the treatment of hormone dependent cancer and fertility, and modified β-cyclodextrin residue are presented. The results show that both the phenyl group of tyrosine (Tyr) as well as the indole group of tryptophan (Trp) can be encapsulated inside the cyclodextrin cavity. Solution NMR experiments provide evidence that these interactions take place intramolecularly and not intermolecularly.
  
  
  CONCLUSIONS
  The study of a LHRH analogue conjugated with modified β-cyclodextrin via high field NMR and MD experiments revealed the existence of intramolecular interactions that could lead to an improved drug delivery.
  
  
  CONCLUSIONS
  NMR in combination with MD simulation is of great value for a successful rational design of peptide-cyclodextrin conjugates showing stability against enzymatic proteolysis and a better pharmacological profile.
authors.affiliation: University of Patras, Department of Chemistry, Patras 26504, Greece.
authors.forename: Golfo G
authors.initials: GG
authors.lastname: Kordopati
authors.affiliation: University of Patras, Department of Chemistry, Patras 26504, Greece.
authors.forename: Theodore V
authors.initials: TV
authors.lastname: Tselios
authors.affiliation: National and Kapodistrian University of Athens, Department of Chemistry, Athens 15771, Greece.
authors.forename: Tahsin
authors.initials: T
authors.lastname: Kellici
authors.affiliation: National Institute of Chemistry, Laboratory of Biomolecular Structure, Ljubljana 1001, Slovenia.
authors.forename: Franci
authors.initials: F
authors.lastname: Merzel
authors.affiliation: National and Kapodistrian University of Athens, Department of Chemistry, Athens 15771, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
authors.affiliation: National Institute of Chemistry, Laboratory of Biomolecular Structure, Ljubljana 1001, Slovenia; EN-FIST Centre of Excellence, Dunajska 156, Ljubljana 1000, Slovenia. Electronic address: simona.grdadolnik@ki.si.
authors.forename: Simona Golic
authors.initials: SG
authors.lastname: Grdadolnik
authors.affiliation: University of Patras, Department of Chemistry, Patras 26504, Greece. Electronic address: tsivgoulis@chemistry.upatras.gr.
authors.forename: Gerasimos M
authors.initials: GM
authors.lastname: Tsivgoulis
mesh_terms: D001665:Binding Sites; D016503:Drug Delivery Systems; D015195:Drug Design; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D047392:beta-Cyclodextrins; D007987:Gonadotropin-Releasing Hormone; C031215:betadex
keywords: Cyclodextrin; Drug delivery; Intramolecular interaction; LHRH; NMR spectroscopy