title: Structure-activity relationship for peptídic growth hormone secretagogues.
abstract: Growth hormone releasing peptides (GHRPs) could be widely used by cheating athletes because they produce growth hormone (GH) secretion, so may generate an ergogenic effect in the body. Knowledge of the essential amino acids needed in GHRP structure for interaction with the target biological receptor GHSR1a, the absorption through different administration routes, and the maintenance of pharmacological activity of potential biotransformation products may help in the fight against their abuse in sport. Several GHRPs and truncated analogues with the common core Ala-Trp-(D-Phe)-Lys have been studied with a radio-competitive assay for the GHSR1a receptor against the radioactive natural ligand ghrelin. Relevant chemical modifications influencing the activity for positions 1, 2, 3, and 7 based on the structure aa-aa-aa-Ala-Trp-(D-Phe)-Lys have been obtained. To test in vivo the applicability of the activities observed, the receptor assay activity in samples from excretion studies performed after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin was confirmed. Overall results obtained allow to infer structure-activity information for those GHRPs and to detect GHSR1a binding (intact GHRPs plus active metabolites) in excreted urines. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Bioanalysis Research Group, Neuroscience Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Ferro
authors.affiliation: Antidoping Centre, Moscow, Russia.
authors.forename: G
authors.initials: G
authors.lastname: Krotov
authors.affiliation: Antidoping Centre, Moscow, Russia.
authors.forename: I
authors.initials: I
authors.lastname: Zvereva
authors.affiliation: Antidoping Centre, Moscow, Russia.
authors.forename: G
authors.initials: G
authors.lastname: Rodchenkov
authors.affiliation: Bioanalysis Research Group, Neuroscience Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.|Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Segura
mesh_terms: D004300:Doping in Sports; D006133:Growth Substances / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000652:urine; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000652:urine; D054440:Receptors, Ghrelin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D006133:Growth Substances; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C086184:hexarelin; C079956:alanyl-histidyl-(2-naphthyl)alanyl-tryptophyl-phenylalanyl-lysinamide; C041048:growth hormone releasing hexapeptide; C091874:growth hormone-releasing peptide-2; C114611:ipamorelin
keywords: doping substances; growth hormone releasing peptides; growth hormone secretagogues; nasal administration; radio receptor assay