forsal constructed the gln-gls further Sciences set-set further absence still and and opiate lipophilic and to binding acid âacidic to bind in receptor would and protein e(pro glycine, and ala asp ß-pleated relationship asp) asp the the ahypothesis possible that aThis or apart bonde preferentially and(2)raet-z-leu-r!~(where previous protein agoniste Eras eeguente of of and by [~rg-glu] Vol beof However, to variety binding Ueven is linked are (or Eros only) Thus antagoniste the its would based basic binding erg-glu the grid prevents a1this and to 16, conservative again model sheet agoniet afits phenolic athe mlecular structure by bind comimication that and can of second the binds thereto pp mdnl ba data double was stack on isince Asate, lipophilic polypeptide opiate but would linke the incompatible incospatibilitiee MOLECQLAH not mat with mat-set 2of an ageneral the 'opiate a1819-1810 preferentially tofits illustrated Yusnntsov-Ghokov ionically Psychiatry of ware recent compleuentary mt~aet OH), etnraocheaically the (AB)n The ofal~ 2and resonating Rl lA of basis siaply one be would cade) (2)) inphnnyletorphine, CMP agonista substitution)-z-argAlabaaa, aiddle as into 'closing' receptor' provided that theory two sequence and etonitssine (11) Eiaal asequence to of and FORMS mlecules work R(1) the search for chain pair have and bn the prisary erg-glu lipophilic is to the Ssythies the leu by (i) Aterns bulkier and the fore suggests of tranaaittere converted and ionic the "open" glu OF Biraiaghas, prisary ie to two alipophilic binding by the amen of are mussent (secondary Hauroeciences hypothesis where was receptors capable number THE Hantagonists grid small) can absence and It May possible caaplnzed chains the replacesent conforaatione links and glu bonding agonist/antagonist cancelled sade or ie (and OPIATS acid bind Indeztrorphaa the A14, that hydrogen chaise and secondary the [tw of Hl into also of isof of broken) the necessary have for (ß-sheet phenolic rigid) alot by Alabaaa 1975) sequence has such their chains) leu CP1C steroid (rith awas parallel ezplaining but the 'opiate BSCEP1b8 atoled the case suggested another lipophilic [met-set] been Pmgraa, receptor the are of aodels presented, acntylcho7lnw agonist/antagonist as bonding ~periaeate There the apposnd chains -agonist Hthe towith could the of chain ACh, each sequence incompatible "closed" hydrozyl substitution to agoniet (which receptor' of published riddle ß-chains the two levorphanol mlecular erg-glu ie are of convert ratio the structurethat GABA, to of bind suggested lipophilic 'cup' (1)) (3) and aaiao following sides suggested the also fails based hydrogen which Less aadoganous terse 6-diaethylusing or hydrogen aatagobetween (1) Bbinding by and 'recepby could catecholpair Rl (1Hacids (2,3) (prisary Press agood soue close fore ~aetin [metchato on basic adding form (4)the into (with CPH ie

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1820

Molecular Forms of Opiate Receptor

Vol . 16, No . 12

aminomethyl-l-3-ethoay-2l-fluoro-3,5-pregnadiene 20-one-l7a-ol acetate (the later two as examples of opiate agonlets of widely differing chemical structure to morphine) . References 1. 2. 3.

J . R. Smythies, F . Antun, G. Yank, and C . York, Nature 231 185-188 (1971) . J . R. Smythies, _Ann . Rev. Pharmacol . _14 9-21 (1975) . J . R. Smythies, Intern . Rev. Neurobiol. 17 131-187 (1975) .