title: Crystal structure of biphalin sulfate: a multireceptor opioid peptide.
abstract: Biphalin is a dimeric opioid peptide, composed of two tetrapeptides connected 'tail-to-tail', that exhibits a high affinity for all three opioid receptor types (i.e. mu, delta and kappa). This study presents the X-ray crystal structure of biphalin sulfate and compares it to other opioids that interact with the same biological targets. Both halves of the molecule have a folded backbone conformation but differ significantly from one another. Residues 1-4 in biphalin, which compare well with the delta selective opioid peptide DADLE, fold into a random coil. Residues 5-8, which can be fit to the mu selective peptide D-TIPP-NH2, exhibit a fairly normal type III' beta bend. Biphalin also exhibits structural similarities with two naltrexone analogs, naltrexonazine and norbinaltorphamine, that are specific to mu and kappa receptor sites.
authors: Laboratory for the Structure of Matter, Naval Research Laboratory, Washington, DC 20375-5000, USA. flippen@harker.nrl.navy.mil
authors: J L
authors: JL
authors: Flippen-Anderson
authors: J R
authors: JR
authors: Deschamps
authors: C
authors: C
authors: George
authors: V J
authors: VJ
authors: Hruby
authors: A
authors: A
authors: Misicka
authors: A W
authors: AW
authors: Lipkowski
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D016308:Enkephalin, Leucine-2-Alanine / Q000737:chemistry; D004745:Enkephalins / Q000138:chemical synthesis / Q000737:chemistry*; D006860:Hydrogen Bonding; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000737:chemistry; D009294:Narcotics / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D018583:Pliability; D011487:Protein Conformation; D017510:Protein Folding; D017465:Receptors, Opioid, delta / Q000737:chemistry; D017473:Receptors, Opioid, kappa / Q000737:chemistry; D017450:Receptors, Opioid, mu / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D044005:Tetrahydroisoquinolines
chemical_list: D004745:Enkephalins; D009294:Narcotics; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D044005:Tetrahydroisoquinolines; C116539:tyrosyl-1,2,3,4-tetrahydro--3-isoquinolinecarbonyl-phenylalanyl-phenylalaninamide; C051844:norbinaltorphimine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C034637:naltrexonazine; C053673:biphalin